Transcript Neurochemistry

Neurotransmitters
•Neuropeptides
•Amines
•Quaternary amines
•Acetylcholine (ACh)
•Monoamines
•Catelcholamines
•Epinephrine (EPI)
•Norepinephrine (NE)
•Dopamine (DA)
•Indoleamines
•Serotonin (5-HT)
•Melatonin
•Amino acids
•Gamma-aminobutyric acid (GABA)
•Glutamate (GLU)
•Glycine
•Histamine (HIST)
•Opioid peptides
•Enkephalins (ENK)
•Endorphins (END)
•Peptide Hormones
•Oxytocin (Oxy)
•Substance P
•Cholecystokinin (CCK)
•Vasopressin (ADH)
•Neuropeptide Y (NPY)
•Hypothalamic Releasing Hormones
•GnRH
•TRH
•CRH
Cholinergic (Ach) System
Alzheimer's: Biology
• chromosomes 1, 14, 19, and 21
• general brain atrophy
• neuronal degeneration
• decreased cerebral metabolism
• general decay of acetylcholine system
– especially in the basal forebrain
• neurofibrillary tangles
• beta-amyloid plaques
General Brain Atrophy
Neuronal Degeneration
Normal
Alzheimer’s
Decreased Cerebral Metabolism
Alzheimer's
Normal
Neurofibrillary
Tangles
Microtubules:
•Provide structural support
•Are pathways for:
•Nutrients
•Waste products
•Neurotransmitters
Made of Tubulin
In Alzheimer’s Disease:
Excess Tau protein binds builds up
Tau binds with Tubulin and tangles the
microtubules preventing them from
properly functioning
Beta-Amyloid Plaque Formation
Key enzymes:
•Alpha-secretase
•Beta-secretase
•Gamma-secretase
Protein fragments:
p3
alpha and gamma
harmless
40 amino acid string
beta and gamma
harmless
42 amino acid string
beta and gamma
TOXIC
Beta-Amyloid Precursor Protein (BAPP)
is cut or cleaved by these enzymes
three different protein fragments form
Beta-Amyloid Plaques
Beta-Amyloid Plaques
Tau Filaments
Pathology:
•Interferes with Ca2+ regulation
•Increases free radicals
•Stimulates microglia aggregation
•Increases inflammation
Noradrenergic (NE) System
Ascending Reticular Activating System
(ARAS)
Arousal
Center
Serotoninergic (5-HT) System
Major
Depressive
Episode
Characteristics
•Onset is in early to mid 20’s
•but not age specific
•Onset age has been dropping
•16% of population experience
MDD in their lifetime
•2:1 women to men ratio
•41% occurs just before or just
after menstruation
Depression and Neurochemistry
Depression
and Stress
Hormones
• cortisol
•steroid hormone
Depression: Treatment
Medical
Chemical
Electroconvulsive Shock Therapy
Psychotherapy
Cognitive Behavioral Therapy
Interpersonal Therapy
Cognitive Behavioral Therapy
•make patient examine thought process and recognize errors
•arbitrary interference
•overgeneralization
•try to correct cognitive errors
•concentrate on less depressive thoughts - be more realistic
•target negative cognitive schemes
•use journals to identify faulty thinking
•do hypothesis testing
•put fun back into the patients life
•increase exercise
•takes about 10-20 sessions
Depressions Vicious Cycle
Must control brain
chemistry
e.g., Prozac
Must reshape the
negative thought
processes
e.g., CBT
Dopaminergic (DA) System
Schizophrenia
Onset can be slow or sudden
Typically exists chronically
Affects ~1% of population
Diagnosis must have at least two symptoms for more that 1 month
Schizophrenia Symptoms
•Positive Symptoms (abnormal states)
•hallucinations (auditory, visual)
•delusions (grandeur, persecution)
•Negative Symptoms (insufficient functioning)
•avolition (inability to initiate/persist in activities)
•alogia (absence of speech)
•anhedonia (inability to experience pleasure)
•affective flattening (flat emotional response)
•Disorganized Symptoms
•inappropriate affect (laughing/crying at the wrong times)
•disorganized speech (illogical, rambling, tangential)
•disorganized behavior (catatonia, agitation/immobility)
Schizophreni
Genetic Risk
by Relatedness
•The Evidence:
•Family History
•Twin Studies
•monozygotic (50%)
•same handed (92%)
•dizygotic (15%)
•both are carriers
•Adopted Children
•more like bioparents
•Single Gene?
•Probably not
Dopamine Hypothesis of
Schizophrenia
Abnormal levels of Dopamine lead to the schizophrenic symptoms
•1. Amphetamine Psychosis
•Chronic users develop schizophrenic symptoms
•paranoia, delusions of persecution, auditory hallucinations
•Amphetamine exacerbates schizophrenic symptoms
•Amphetamines promote the release of catelcholamines
•particularly dopamine
•2. Antipsychotic Drugs
•chlorapromazine is a dopamine antagonist and antipsychotic
•block specifically D2 and D4 receptors in the limbic system
•effectiveness is related to magnitude of blockade
•3. Parkinson’s Disease
•some patients receiving L-dopa become psychotic
•some schizophrenic patients on antipsychotics develop Parkinson’s symptoms
Chemical
Messengers
•Autocrine
•self signal
•Paracrine
•neighbor signal
•Endocrine
•distant signal
•Pheromone
•airborne signal
•same species
•Allomone
•airborne signal
•different species
Endocrine System
Homeostasis
Mechanism
Receptors
input signals
skin responds to cold
temperature
sends signal to brain
Control Center
integrating center
brain interprets temp signal
makes you shiver
Effectors
output mechanism
muscles shiver creating heat
Negative
Feedback
Results in an immediate reversal
of the imbalanced system
Immediately negates the
disruption
Most systems in the body work
via negative feedback systems
temperature
glucose balance
water balance
blood pressure
Positive
Feedback
Immediate further disruption of the
imbalance so as to later return to
homeostasis
childbirth
ovulation
Positive Feedback: Childbirth
Posterior
Pituitary
Hormones synthesized in the
hypothalamus
Released by the posterior pituitary
•Oxytocin
•milk ejection
•orgasm
•Vasopressin or ADH
•water balance
•blood pressure
Anterior
Pituitary
Releasing hormones synthesized
in the hypothalamus
•CRF/CRH
•GnRH
•GHRH
•TRH
•PRH
Triggers hormone release in
anterior pituitary
•ACTH
•LH/FSH
•GH
•TSH
•PRL