Psychmentor notes Flashcards
Action Potential
Action potentials
resting state and the inside of the cell is NEGATIVELY charged with respect to the outside. (-70mV)
due to a HIGH concentration of Na+ outside compared to the K+ inside the cell. maintained by the Na/K pump.
For an action potential to take place first the membrane potential must be raised to about -55mV.
This is done by a neurotransmitter binding to the postsynaptic neuron and opening some ion channels.
Once it reaches -55mV it initiates an irreversible process whereby a large number of Na channels open and cause the cell to DEPOLARISE.
Once the membrane potential reaches about +40 the Na channels close
K gates open, the K floods out and the membrane potential falls back again.
Alcohol metabolism
Alcohol is also oxidised by the cytochrome system (CYP2E1, 1A2, and 3A4) and enzyme - catalase.
The three different class I gene loci,
ADH1A (alpha), ADH1B (beta), and ADH1C (gamma)
close to each other region 4q2123.
alleles ADH1C1 and ADH1B2 = fast metabolism of alcohol
ADH1B*2 (fast) is the most common allele in Asian populations
ADH1B1 slow allele is very common among Caucasians-
95 percent homozygous ADH1B1/1
5 percent = heterozygous ADH1B1/2 genotype.
ADH1B1 (slow) most common in africans
There is one significant polymorphism of the ALDH2 gene—> allelic variants ALDH21 + ALDH22 = virtually inactive.
ALDH2*2 in 50 percent of the Taiwanese, Han Chinese, and Japanese populations
FUNCTION OF ALPHA SECRETASE
Alpha-secretase
cleaves APP —non toxic
beta and gamma secretase cleave APP–> shorter, stickier fragments = beta-amyloid–>insoluble amyloid plaques
ALZHEIMERS GENETICS
APP 21
PSEN-1 14
PSEN-2 1
APOE 19
APOE is thought to be involved in the breakdown of amyloid plaques
homozygous for the E4 =10 and 30 times increased risk
Heterozygotes for APOE4 = 3 times increased risk
The presenilins are components of enzymes (alpha secretase) that cleave APP to produce amyloid beta fragments of different lengths. Alterations in the ratios of these fragments can result in insoluble amyloid leading to plaque formation
(familial) Alzheimer’s is very rare and account for only 0.1% of all Alzheimer’s cases.
AUTISM AND MACROCEPHALY
macrocephaly in 20%
not present at birth
AUTISM
AUTISM
MZ 60% DZ 10%
MALE: FEMALE 4:1
BBB AND circumventricular organs
circumventricular organs (BBB fenestrated here) and include:-
Pineal body
Posterior pituitary**
Area postrema**
Subfornical organ
Vascular organ of the lamina terminalis
Median eminence
Molecules that are highly charged struggle to pass through Nasally administered drugs can theoretically bypass the BBB Endothelial cells (caps) are joined by tight junctions
BASAL GANGLIA
LIMBIC SYSTEM
BASAL GANGLIA
control of movement and cognition striatum = caudate, putamen, NA subthalmic nucleus globus pallidus GB and PUT - LENTICULAR NUCLEUS
SN (pars compact and pars reticulate) - in midbrain
movement, reward, addiction, mood
LIMBIC SYSTEM
emotion, behaviour, and memory.
Amygdala Hippocampus Anterior thalamic nuclei Septum, Limbic cortex Fornix
OTHER
akinetic mutism = damage to the mesial frontal lobes, specifically the cingulate gyrus and the supplementary motor area
new semantic knowledge impaired = damage to medial temporal lobe = hippocampal region,entorhinal, perirhinal, and parahippocampal cortices.
CATECHOLAMINES STRUCTURE
Catecholamines
Catecholamines have a unique structure of:
benzene ring with two hydroxyl groups,
an intermediate ethyl chain,
and a terminal amine group.
CELL CYCLE
Prometaphase - The nuclear membrane dissolves and microtubules become attached to the centromeres
Interphase:
G1 (Gap 1) - preparing the cell for DNA SYTHESIS.
S (synthesis) - DNA REPLICATION occurs during this stage
G2 (Gap 2) - preparing the cell for MITOSIS
CENTROMERES
Chromosomes with very small P arms are called acrocentric.
Acrocentric chromosomes can be involved in Robertsonian translocations.
metacentric- equal arms
sumetacentric- unequal
telocentric- right at terminal end, house mouse, NOT IN HUMANS
During a Robertsonian translocation, the participating chromosomes break at their centromeres and the long arms fuse a single centromere. The short arms also join to form a reciprocal product.
occurs on 13, 14, 15, 21, 22
Chimeras and mosaics
plasmid = autonomously replicating, extrachromosomal circular DNA molecule, distinct from the normal bacterial genome and nonessential for cell survival
morula= spherical embryonic mass of blastomeres formed before the blastula and resulting from cleavage of the fertilized ovum.
Mosaics (originate from single zygote) and chimera (originate from more than one zygote) = presence of two or more populations of cells with different genotypes in one individual
e.g. from non-disjunction (dont seperate in anaphase), anaphase lag and endoreplication
sequences and amino acids - codons
CODONS
64 sequences
20 amino acids
10 essential
COPY NUMBER VARIATIONS
Portions of DNA have been found to vary in number due to copies and deletions of portions
- -> additional or fewer copies of certain genes
- -> effect expression of certain genes
most not clinical significant but accoc with:
autism, schizophrenia, and idiopathic learning disability
Cranial foramina
Foramen spinosum Middle fossa Middle meningeal artery*
Foramen ovale Middle fossa Mandibular nerve
Foramen lacerum Middle fossa Internal carotid artery*
Foramen magnum Posterior fossa Spinal cord
Jugular foramen Posterior fossa CNs IX, X, and XI
CRANIAL FOSSA
Anterior cranial fossa: frontal lobes, frontal and ethmoid bones, and the lesser wing of the sphenoid.
Middle cranial fossa: temporal lobes and bones, greater wing of the sphenoid, sella turcica,
Posterior cranial fossa: occipital lobes, cerebellum, and medulla and includes the occipital bone.
Creutzfeldt-Jakob disease
DHAT is a culture bound syndrome seen in Indian men.
men are anxious that they are passing semen in their urine and so are depleted of energy.
Prion diseases including; scrapie, BSE, and Kuru.
vCJD CJD
Duration (from onset of symptoms to death) Longer, a year or more Shorter, few months
MRI Pulvinar sign Bilateral anterior basal ganglia high signal
EEG Generalised slowing Biphasic and triphasic waves 1-2 per second
***Variant CJD is the only form of CJD that affects the lymph nodes. Therefore a tonsillar biopsy is used to support a diagnosis.
PULVINER SIGN= bilaterally hyperintense pulvinar nuclei of the thalamus/medial aspects on FLAIR or diffusion-weighted MRI images (CT is usually normal).
sensitivity of 78% -90%, specificity of 100% for vCJD
DDX =
Alper’s Syndrome,
cat-scratch disease
post infectious encephalitis.
M/V2 subtype of sporadic CJD,
thalamic infarctions,
top-of-the-basilar ischemia
Dementia pugilistica
‘punch drunk syndrome’
Symptoms of may include; ataxia, slurred speech, impaired hearing, tremors, disequilibrium, neurobehavioral disturbances, progressive cognitive decline.
Behavioral signs: aggression, hypertension, suspiciousness, paranoia, childishness, hypersexuality, depression, and restlessness. THEN; impulse control, irritability, inappropriateness, and explosive outbursts of aggression.
Neuropathological: neurofibrillary tangles*****(most prev pathaology),
neuritic plaques, cerebral infarcts,
fenestrated septum pellucidae,
atrophic and gliotic mammillary bodies,
pale substantia nigrae and locus ceruleae,
thalamic gliosis, loss of Purkinje cells in the cerebellum,
cerebral and cerebellar atrophy and lesions
fornix degeneration and degradation.
Damage to the superior cerebellar peduncle and red nucleus ——> slurring dysarthria and tremors.
Substantia nigral degeneration and neuronal loss in the lentiform nucleus—–> Parkinsonian symptoms
Cortical atrophy, specifically in the temporal lobe——-> hypersexual behavior LIKE in Kluver-Bucy syndrome.
septum pellucidum damage —–> depression
mamillary bodies and the fornices ——–> inappropriate emotions and abrupt mood changes, and is consistent with the symptoms of Wernicke-Korsakoff syndrome.
NFTs in normal part of aging, in the hippocampus and temporal lobe. uncommon in the neocortex
DEPRESSION NEUROIMAGING
Amygdala volume decreases significantly with increasing number of episodes
PET: elevated baseline amygdala activity in depression ~ severity
greater amygdala reactivity to emotional stimuli,(esp negative)
increased activity subgenual anterior cingulate cortex (ACC) but decreased volume
less dorsolateral prefrontal cortex (DLPFC) reactivity to affective stimul
DEPRESSION POST STROKE
POST STROKE DEPRESSION (30-40%)
paticularly leisions left basal ganglia
SSRIs (fluox, cital - esp if on warfarin)
Mirtazapine
Nortriptyline
effective in prophylaxis:
Nortriptyline Mirtazapine Fluoxetine Escitalopram Sertraline
NON DOMINANT PARIETAL
NON DOMINANT PARIETAL
Anosognosia (inability to recognise one’s own illness)
Hemisomatognosia (neglect of half the body)
Dressing apraxia
Prosopagnosia (inability to recognise faces)
DURA MATER AND ITS FOLDS
dura–>arachnoid–>pia
folds/seperations of dura
Falx cerebri - cerebral hemispheres
Tentorium cerebelli - cerebellum from the cerebrum
Falx cerebelli - cerebellar hemispheres
Sellar diaphragm - covers the pituitary gland and forms a roof over the hypophysial fossa
DYSARTHRIA
DYSARTHRIA
Spastic Explosive and forceful, at a slow rate Pseudobulbar palsy, spastic hemiplegia
Flaccid Breathy, nasal voice, imprecise consonants Myasthenia gravis
Hypokinetic Slow, quiet, with a tremor Parkinson’s disease
Hyperkinetic Variable rate, inappropriate stoppages, strained quality Huntington’s disease, Sydenham’s chorea, tardive dyskinesia
Ataxic Rapid, monopitched, slurred Friedreich’s ataxia, alcohol abuse
PICKS DISEASE/ FTLD
PICKS DISEASE/ FTLD
3RD most common dementia
macro: atrophy temp and frontal
micro: pick bodies (TAU), gliosis, NF tangles, senile plaques, balloon cells = state of c. degeneration
Focal gyral atrophy with knife-blade appearance- gyri are thin, narrow and resemble knives.
There are three recognised types of FTLD
1.Frontotemporal dementia (Pick’s)
hyperorality, disinhibition, increased appetite, and perseveration behaviour
2.Progressive non fluent aphasia (chronic progressive aphasia, CPA)
non fluent speech. utterances, agramatic, comprehension ok
3.Semantic dementia
fluent aphasia, empty speech. memory BETTER for recent rather than remote
Hirano bodies are seen in a number of conditions including Alzheimer’s and Pick’s disease
genetic mapping
Gene mapping
- Genetic mapping - uses techniques such as pedigree analysis.
- Physical mapping - uses molecular techniques to cut the DNA into pieces (using restriction enzymes) then to look at the pattern of pieces that result/used to sequence DNA
Physical maps can be divided into three general types (vary in resolution): chromosomal or cytogenetic maps, radiation hybrid (RH) maps, sequence maps
three fissures
LANDMARKS
The medial longitudinal fissure - right and left hemispheres
The lateral sulcus/Sylvian fissure - this divides the frontal and parietal lobes above from the temporal lobe below
The central sulcus/ fissure of Rolando - this separates the frontal from the parietal lobe
gyri
superior frontal Precentral Postcentral Angular Fusiform Superior temporal Lingual Cingulate Parahippocampal Dentate
Superior frontal Frontal lobe Laughter and self awareness
Precentral Frontal lobe Voluntary movement control
Postcentral Parietal lobe Touch
Angular Parietal lobe Language, mathematics and cognition
Fusiform Temporal lobe Face and body recognition, word and number recognition (visual)
Superior temporal Temporal lobe Launguage (Wernicke’s area), and sensation of sound
Lingual Occipital Dreaming, word recognition (visual)
Cingulate Adjacent to the corpus callosum Emotion, learning, and memory
Parahippocampal Surrounds the hippocampus Memory (also asymmetry has been observed in schizophrenia)***
Dentate Hippocampus Formation of episodic memory
HISTAMINE
Histine—>histidine decarboxylase—> histamine—> histamine methyltransferase and MAO
H1 CNS tissue, smooth muscle, and endothelium
Vasodilation, bronchoconstriction, pain and itching from stings
H2 Parietal cells in stomach
Stimulates gastric acid secretion
H3 Central and peripheral nervous tissue
Decreases the release of other neurotransmitters (serotonin, noradrenaline, acetylcholine)
H4 Basophils
Chemotaxis (cellular movement)
