This document provides an overview of animal models used to study anti-convulsant drugs. It discusses several chemical and electrical induced seizure models used in mice and rats, including pentylenetetrazol, picrotoxin, strychnine, bicuculline, electroshock, and lithium-pilocarpine induced status epilepticus. The models aim to mimic different types of human seizures and evaluate potential anti-convulsant drugs by measuring changes in seizure threshold, motor pattern, EEG patterns, and seizure incidence. Genetic models like totterer mice that spontaneously develop seizures are also described.
Explanation of Preclinical (Animal) Models of Seizure and Epilepsy.
General overview of Seizure and Epilepsy and its current Management. Need to develop newer drugs and Newer models. Current models for Acute Seizure. Kindling explained. PPT contains overview and Protocol.
Explanation of Preclinical (Animal) Models of Seizure and Epilepsy.
General overview of Seizure and Epilepsy and its current Management. Need to develop newer drugs and Newer models. Current models for Acute Seizure. Kindling explained. PPT contains overview and Protocol.
Screening methods of Anti epileptic drugs.
Different methods to induce Experimental epilepsy.
Physical and chemical types of screening model of epilepsy.
Screening methods of Anti epileptic drugs.
Different methods to induce Experimental epilepsy.
Physical and chemical types of screening model of epilepsy.
Anti epileptic drugs screening methods including invitro and invivo screening methods includes isoniazid picrotoxin strychrinine and Pentenlytetrazole induced convulsion
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
Slide 1: Title Slide
Extrachromosomal Inheritance
Slide 2: Introduction to Extrachromosomal Inheritance
Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus.
Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids.
Slide 3: Mitochondrial Inheritance
Mitochondria: Organelles responsible for energy production.
Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria.
Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring.
Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy.
Slide 4: Chloroplast Inheritance
Chloroplasts: Organelles responsible for photosynthesis in plants.
Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts.
Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species.
Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA.
Slide 5: Plasmid Inheritance
Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes.
Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation.
Significance: Important in biotechnology for gene cloning and genetic engineering.
Slide 6: Mechanisms of Extrachromosomal Inheritance
Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance.
Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells.
Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression.
Slide 7: Examples of Extrachromosomal Inheritance
Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells.
Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration.
Slide 8: Importance of Extrachromosomal Inheritance
Evolution: Provides insight into the evolution of eukaryotic cells.
Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases.
Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification.
Slide 9: Recent Research and Advances
Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA.
Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases.
Slide 10: Conclusion
Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology.
Future Directions: Continued research and technological advancements hold promise for new treatments and applications.
Slide 11: Questions and Discussion
Invite Audience: Open the floor for any questions or further discussion on the topic.
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
What is greenhouse gasses and how many gasses are there to affect the Earth.moosaasad1975
What are greenhouse gasses how they affect the earth and its environment what is the future of the environment and earth how the weather and the climate effects.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
Deep Behavioral Phenotyping in Systems Neuroscience for Functional Atlasing a...Ana Luísa Pinho
Functional Magnetic Resonance Imaging (fMRI) provides means to characterize brain activations in response to behavior. However, cognitive neuroscience has been limited to group-level effects referring to the performance of specific tasks. To obtain the functional profile of elementary cognitive mechanisms, the combination of brain responses to many tasks is required. Yet, to date, both structural atlases and parcellation-based activations do not fully account for cognitive function and still present several limitations. Further, they do not adapt overall to individual characteristics. In this talk, I will give an account of deep-behavioral phenotyping strategies, namely data-driven methods in large task-fMRI datasets, to optimize functional brain-data collection and improve inference of effects-of-interest related to mental processes. Key to this approach is the employment of fast multi-functional paradigms rich on features that can be well parametrized and, consequently, facilitate the creation of psycho-physiological constructs to be modelled with imaging data. Particular emphasis will be given to music stimuli when studying high-order cognitive mechanisms, due to their ecological nature and quality to enable complex behavior compounded by discrete entities. I will also discuss how deep-behavioral phenotyping and individualized models applied to neuroimaging data can better account for the subject-specific organization of domain-general cognitive systems in the human brain. Finally, the accumulation of functional brain signatures brings the possibility to clarify relationships among tasks and create a univocal link between brain systems and mental functions through: (1) the development of ontologies proposing an organization of cognitive processes; and (2) brain-network taxonomies describing functional specialization. To this end, tools to improve commensurability in cognitive science are necessary, such as public repositories, ontology-based platforms and automated meta-analysis tools. I will thus discuss some brain-atlasing resources currently under development, and their applicability in cognitive as well as clinical neuroscience.
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
THE IMPORTANCE OF MARTIAN ATMOSPHERE SAMPLE RETURN.Sérgio Sacani
The return of a sample of near-surface atmosphere from Mars would facilitate answers to several first-order science questions surrounding the formation and evolution of the planet. One of the important aspects of terrestrial planet formation in general is the role that primary atmospheres played in influencing the chemistry and structure of the planets and their antecedents. Studies of the martian atmosphere can be used to investigate the role of a primary atmosphere in its history. Atmosphere samples would also inform our understanding of the near-surface chemistry of the planet, and ultimately the prospects for life. High-precision isotopic analyses of constituent gases are needed to address these questions, requiring that the analyses are made on returned samples rather than in situ.
2. INTRODUCTION-
Anticonvulsants (also commonly known as antiepileptic
drugs or as antiseizure drugs) are a diverse group
of pharmacological agents used in the treatment
of epileptic seizures.
Anticonvulsants are also increasingly being used in the treatment
of bipolar disorder and borderline personality disorder.
Epilepsy is a group of disorders of the CNS characterised by
proximal cerebral dysrhythmia, manifestation as brief
episode(seizures)of loss or disturbance of consciousness, with
or without characteristic body movement(convulsion),sensory
or psychiatric phenomena.
It is a very common disorder, characterised by seizures.
3. SEIZURE TYPE FEATURES CONVENTIONAL
ANTISEIZURE
DRUGS
RECENTLY
DEVELOPED
ANTISEIZURE
DRUGS
1.Partial
seizures
a)Simple partial Diverse
manifestations
determined by the
region of cortex
activated by the
seizurelasting.Its last
for
20 to 60 sec.Key
feature is
preservation
Carbamazepine,
phenytoin,
valproate
Gabapentin,
lamotrigine,
levetiracetam,
tiagabine,
topiramate,
zonisamide
b)Complex
partial
Impaired
consciousness lasting
30sec to 2min,often
Carbamazepine,
phenytoin,
valproate
Gabapentin,
lamotrigine,
levetiracetam,
Classification
4. 2.Generalized
seizures:
a)Absence
seizure
Abrupt onset of
impaired
consciousness
associated with
staring & cessation
of ongoing activities
typically lasting
less than 30 sec
Ethosuximide,
valproate
Lamotrigine
b)Myoclonic
seizure
A brief (perhaps a
sec), shock like
contraction of
muscles which may
be restricted to part
of one extremity or
may be generalized
Valproate Lamotrigine,
topiramate
c)Tonic-clonic
seizure
It is not preceded by
a partial seizure
Carbamazepine,
phenobarbital,
phenytoin,
primidone,valproat
e
Lamotrigine,
topiramate
6. ANIMAL MODELS OF SEIZURE
The animal model are essential in the pre-clinical research of
new drugs to develop new treatment approaches for epileptic
seizures.
The drug effect chosen for the study can be assessed on
following parameters:
i. Change in the threshold,
ii. A qualitative change in pattern of the motor
seizure,
iii. Changes in the EEG pattern,
iv. Change in incidence of seizures.
7. ANIMAL MODEL OF SEIZURE
Animal Model of Seizure
Genetic rat model
of epilepsy
Electroshock
seizure
Chemical
induced model
Kindled rat
seizure model
Chemical
induced model
Pentylenetetrazol
(PTZ) induced
seizure
Strychnine
induced seizure
Picrotoxin induced
seizure
Isoniazid induced
seizure
Bicuculine
induced seizure
8. 1.Electroshock Seizures In Mice & Rats
Protection against electroshock induced seizures in mice and rats
is used as an indication for compounds which may prove effective
in
Electric stimuli evoke tonic hind limb extensions, which are
suppressed by anti-epileptic drugs.
Types of electroshock seizures
Supramaximal Electroshock.
Extensor Seizure Latency.
Psychomotor Electroshock.
Minimal Electroshock Threshold.
9. Procedure :-
Tonic clonic convulsions are produced in mice or rats.Through
high electroshock currents by placing electrodes on the ears.
Purpose- induce the most intense physiologically possible seizure by
a method analogous to human electroshock therapy.
Current used:
oRat : 150mA
oMice : 50 mA 0.2 second duration
10. Chemical induced seizures :
i)Pentylenetetrazol(PTZ)induced seizures
Purpose : Pentylenetetrazole Produces convulsion similar to
petitmal type of convulsion in rats and mice.
Procedure:
FIRST GROUP SECOND GROUP
INJECTED-Diazepam
4mg/kg(i.p)
control
Two groups of 10 Albino Swiss mice of either sex (20-25 gm)
30min after Diazepam treatment inject with 75 mg/kg of PTZ by s.c.
Each animal is observed for 1 hr. in plastic cage
11. II)ISONIAZID INDUCED CONVULSIONS
Purpose :
Isoniazid is a GABA synthesis inhibitor.
It produce convulsions in patients having history of seizures.
Procedure:
o Two groups each of 10 albino mice (18-22gm)
o 15 min after s.c. injection/30min after i.p./60 min after oral route, 300 mg/kg
of INH is injected by s.c. to the both groups.
o During next 120 minutes clonic seizure, tonic seizure and death is recorded.
Parameter to be Evaluate:
Status of animal after 30 minutes.
Status of animal after 24 hour.
Percentage protection
11
FIRST GROUP SECOND GROUP
INJECTED-Diazepam 5mg/kg. (i.p.) as control, receive saline.
12. III)PICROTOXINE INDUCED CONVULSIONS
Purpose : Picrotoxin is regarded as GABAA-Antagonist modifying the
function of chloride ion channel of GABAA receptor complex.
Procedure:
Two groups of 10 Albino mice of either sex (18-20 gm)
First group is treated with 5mg/kg Diazepam i.p.
Second group is treated with normal saline, as control group
15mins after i.p. inject 3.5 mg/kg of Picrotoxin through i.p. route
Observe the symptoms during next 30 min.
Parameter to be Evaluate:
Status of animal after 30 minutes.
Status of animal after 24 hour.
Percentage protection
12
13. IV)STRYCHNINE INDUCED CONVULSIONS
Purpose:
The convulsive action of strychnine is due to interference with post
synaptic inhibition mediated by glycine.
Strychnine act as selective and competitive antagonist to block
inhibitory effect of glycine to all glycine receptors.
Procedure:
Two groups of 10 Albino mice of either sex (18-20 gm)
First group receive 5mg/kg Diazepam i.p.
Second group is control, receive normal saline.
One hour later, mice are injected with 2mg/kg strychnine (i.p.)
Observe the symptoms during next 30 min.
Parameter to be Evaluate:
Status of animal after 30 minutes.
Status of animal after 24 hour.
Percentage protection
13
14. VI)BICUCULINE TESTS IN RATS
Purpose : Bicuculine antagonize the action of GABA by competition on
postsynaptic receptor and induces Myoclonic Seizure.
Procedure:
Two groups of 10 Albino mice of either sex (18-20 gm)
First group is treated with 5mg/kg Diazepam i.p.
Second group is treated with normal saline, as control group
15mins after i.p. inject 1 mg/kg of Bicuculine through i.v. route
Observe the symptoms during next 30 min.
Parameter to be Evaluate:
Status of animal after 30 minutes.
Status of animal after 24 hour.
Percentage protection
15. STATUS EPILEPTICUS
Different animal models used are:
pilocarpine induced status epilepticus.
Lithium pilocarpine induced status epilepticus.
Lithium methomyl induced seizure in rats.
Electrical stimulation of hippocampal perforant pathways.
15
16. CHEMICAL INDUCED STATUS EPILEPTICUS
Pilocarpine
Cholinomimetic
Can produce status epilepticus in rats
Dose : 380-400 mg/kg
Route : ip
Lithium- Pilocarpine;
Pretreatment with lithium – 3meq/kg ip
Followed by pilocarpine – 30-40 mg/kg ip
Lithium – methomyl
Pretreatment with lithium
Methomyl – 5.2mg / kg s.c.
16
17. GENETIC ANIMAL MODEL FOR EPILEPSY
Totterer Mice:
Homozygous strain totterer mice are prone to spontaneous
epileptic seizure
Broad based ataxic gate
By 3 to 4 weeks of age → develop frequent partial seizure
Spontaneous focal motor seizure occur a few times a day →
unilateral clonic jerk of limbs with secondary generalization
Also exhibit absence seizure with synchronous 6-7 per second
spike wave discharges in EEG
Two seizure type in one model
17
18. CONCLUSION
Ideal model of epilepsy should show the following characteristics
Development of spontaneously occurring seizures
Type of seizure similar to that seen in human epilepsy
EEG correlates of epileptic –like activity
Age dependency in the onset of epilepsy as seen in many
epileptic syndromes
At present no model follows all criteria
Only genetic model come close
The antiepileptic drug development program primarily based
on two seizure model, the MES and the PTZ.
Single method of screening of antiepileptic drugs can not predict
the full pharmacological profile of the drug.
18
19. Reference:
1.Experiment modeling of anxiety.(by- Nimish L.Pathak,Sanjay
B.Kasture,Nayna M.Bhatt and Ritesh
G.Patel)www.japsonline.com
2.Manual of pharmacology and therapeutics-Goodman & Gilman's
3.Drug discovery and evaluation(pharmacological assays-2nd
edition)-H.Gerhard Vogel
4.S. K. Kulkarni, Handbook of Experimental Pharmacology.
5.S.K Gupta, text book of screening methods and toxicology, page no:401-
419
6.Tripathi KD, Essentials of medical pharmacology, 6th edition, chapter-7
page no:401-413
7.N S Parmar, screening methods of pharmacology, chapter-5 page no:90-
97