ANA 442 Exam 3 (Answered) 2022 Graded A+ PD as not just a disease of DA neurons
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Course
ANA 442
Institution
ANA 442
Midbrain/brainstem and some peripheral
DA neurons of SN and VTA
5-HT neurons of brainstem, descending projections
NE neurons of LC
Substance P, ACh, Vagal nerves
ALL SEEM TO BE LIGHTLY MYELINATED
Clinical PD
Bradykinesia
Rigidity
resting tremor
gait changes
Biochemistry of PD
80% loss o...
PD as not just a disease of DA neurons
Midbrain/brainstem and some peripheral
DA neurons of SN and VTA
5-HT neurons of brainstem, descending projections
NE neurons of LC
Substance P, ACh, Vagal nerves
ALL SEEM TO BE LIGHTLY MYELINATED
Clinical PD
Bradykinesia
Rigidity
resting tremor
gait changes
Biochemistry of PD
80% loss of DA in caudate/putamen
Pathology of PD
50% loss of DA neurons in Pars Compacta (SN)
Premotor Phase of PD
constipation- gut alpha synuclein, smell, cardiac, sleep disturbances
Anticholinergics for PD
treat the resting tremor, avoid in older patients
MAO-B inhibitors
prevents metabolism of DA, fairly well-tolerated but with little efficacy
PD Non-motor manifestations and their associated neurobiology
PNS: pain, constipation
Spine: orthostatic hypotension
Brainstem: anxiety, depression, sleep dist.
Cortical: cognitive deficits, psych disorders, anosmia
Ideal animal model of PD
1. human brain anatomy (both caudate and putamen)
2. clinical symptoms (motor and non-motor)
3. neuropathology: lose DA neurons + Lewy bodies
4. Neurochemistry: striatal DA depletion
5. behavioral response to L-DOPA
Invertebrate models of PD
fruit fly: molecular and cellular
roundworm: genetic and molecular
Zebrafish PD
MPTP elucidates genetic pathways, is responsive to DA mimetics
Mice and rats PD model
, unilateral: 6-OHDA
bilateral: systemic MPTP or Rotenone
Toxicity mechanisms for PD
6-OHDA: taken up by DA transporter, generates free radicals
rotenone: C1 inhibitor
MPTP: turned into MPP+, taken up into mitochondria, leading to C1 inhibition and free
radical formation
6-OHDA animal model behavior
d-amphetamine: DA released, ipsilateral turning
APO (apomorphine): DA receptor agonist, contralateral turning
6-OHDA weaknesses and benefits
benefits: cheap, DA cell loss, motor deficits, reponds to DA mimetics
weakness: 6-OHDA doesn't cross BBB, rat basal ganglia different than human, rapid
and non-progressive, young animals, no Lewy bodies
MPTP rodents adv. and weaknesses
advantages: cheap, BBB, DA cell loss
Disadvantages: not all strains of mice are susceptible to MPTP, sometimes
spontaneous recovery
MPTP monkey model
adv: similar basal ganglia, motor and cognitive deficits
disadvantages: expensive, non-progressive, spontaneous recovery, no lewy bodies,
non-motor deficits
PTSD core features
emotional numbing, hyper-arousal, re-experiencing, avoidance
re experiencing in PTSD
recurrent and intrusive recollection, dreams, feeling event is happening, distress at
symbolism
avoidance features of PTSD
don't want to think of incident, literally forget, avoid hoomans and stuff
arousal features of PTSD
sleepless, irritability, anxiety, hypervigilence, poor concentration, startle response
DSMV PTSD
2 of the following:
intrusion, avoidance, negative alterations in cognition, alterations in arousal
Risk events for PTSD
rape, assault, shoot/stab, death of family, witness killing, natural disaster
Fight or flight neurobiology
NE and epi release, locus coerulus firing, amygdala
HPA neurobiolgy
hypothalamus releases corticotropin releasing hormone
pituitary releases adrenocorticotrophic hormone
this all increases cortisol levels
physiological markers of PTSD
autonomic increase
increased baseline HR and BP
increased resting HR in traumatized children
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