Addiction + neurodegenerative/neurological disorders

Addiction involves dysfunction in what 3 things?

PFC, basal ganglia, and dopamine system

Addiction is driven by what kind of learning?

How is dopamine involved?

Reinforcement learning - drugs increase dopamine signaling (especially in nucleus accumbens) and dopamine = reinforcement

faster dopamine increase = higher addiction risk

3 ideas behind treating addiction:

Block the receptor

• naloxone reverses overdoes

• naltrexone reduces drug effects)

Maintenance therapy

• methadone and buprenorphine

Brain stimulation (experimental)

• TMS / DBS

What is a stroke?

• Ischemic vs Hemorrhagic

Stroke = sudden interruption of blood supply to the brain, often cause perminant brain damage (but that depends on size of blood vessel and how long from start to treatment)

Ischemic = blocked artery (blocking blood flow)

Hemorrhagic = Ruptured artery (bleeding around the brain)

• when pressure in artery builds up it can cause wal of blood vessel to rupture)

Stroke treatment: Ischemic vs Hemorrhagic

Ischemic - “clot-busting” drugs (thrombolytics) - short time window (3-4 hrs) OR “clot removal” (thrombectomy)

Hemorrhagic - surgery to repair blood vessel + blood pressure management

TBIs: closed vs open head injuries

Closed (concussions) → caused by blow to head with blunt object

Open → caused by penetrating brain injuries - damages blood vessels, increases pressure and leads to inflammation

What is a Seizure? What are some possible causes?

Sudden, uncontrolled electrical disturbances in the brain

Brain scarring; withdrawal of GABA agonist, gene mutations, high fevers (in children), or idiopathic (unknown)

Partial vs Generalized (2 types) seizures

Partial = starts and stays in one part of the brain

• “simple” = stay conscious; “complex” = loose consciousness

Generalized seizures = involves most of the brain + always loss of consciousness

• Grand Mal (tonic-clonic) = have an “aura” (can sense them coming); Tonic = intense muscular contraction followed by Clonic = Violent rhythmic contractions

• Petit Mal (absent) = “spells of absence” - stare off into distance, blinking repeatedly; short (10 seconds)

Seizure disorder treatments

Anticonvulsant drugs → Benzodiazepines (increase GABA’s inhibitory effects on the brain)

Most ppl respond well to meds but if that doesn’t work surgery can help

What is a Brain Tumor? How do they damage brain tissue?

Mass of cells w/ uncontrolled growth that serve no useful function

Damage brain tissue w/ either compression or infiltration

Non-malignant vs Malingant brain tumors

• Distinct boarder?

• Easy to remove?

• Can it metastasize?

Non-malignent = Benign (distinct border); encapsulated → can be removed; can not metastasize (spread)

Malignant = Cancerous (no distinct boarder); infiltrates surrounding tissues → difficult to remove; can metastasize (spread)

Meningiomas vs Gliomas (brain tumors)

Meningiomas = non-malignant; start within tissue of meninges; easier to remove

Gliomas = malignant; arise from natural stem cells that give rise to glia cells; grow/divide quickly (hard to remove); resistant to chemotherapy/radiation

Brain infections: Meningitis vs Encephalitis

M = inflammation of the meninges due to bacteria or virus; first symptoms = headache, stiff neck

E = Inflammation of brain itself due to bacteria/virus/toxic chemicals/allergic reactions; first symptoms = headache, nausea, fever

Brain infections - effects of environmental toxins

Things like insecticides, heavy metals (lead/mercury), alcohol

impairment of fetal development = intellectual disability

Fetal alcohol syndrome

Alcohol consumption in 3rd-4th week of pregnance = premature birth, smaller birth size, distinct facial features, delayed development

Inherited Metabolic Disorders vs Congenital disorders

IMD - “inborn errors in metabaolism” caused by gene mutations that disrupt code for enzyme synthesis (absence of enzyme)

CD = present at birth

Phenylketonuria (PKU) vs Tay-Sachs Disease

• Absence of enzyme x

• Leads to?

Both are Inherited Metabolic Disorders

PKU = absence of enzyme that converts phenylalanine to tyrosine → brain damage + Low-phenylalanine diet

Tay-Sachs = Absence of enzyme in lysosomes → waste buildup → cell and brain swelling → brain damage (fatal)

Down Syndrome

Congenital (present at birth); caused by extra 21st chromosome

Fetal development impairment = intelectual disability + distinct facial features

Also, increased risk of alzheimers (especially after 30)

Multiple Sclerosis (MS)

• Damages what (leading to)…?

• Symptoms (remitting-relapse vs progressive)

• Treatment

Autoimmune disorder that makes immune cells attack myelin sheath, leading to scarring, plaques and interrupting action potentials →

Remitting-relapse MS = cycles of flareups and recindings (gradually getting worse over time)

Progressive MS = slow continuous increase in symptoms and disease progression

Treatment = NO CURE but…

• Monoclonal antibodies help make immune system attack immune cells that attack myelin

• other drugs limit movement of immune cells into the CNS

Neurodegenerative Diseases are a result of what? Which is triggered by what?

Cellular apoptosis (cell death) → triggered by aggregates (clumps) of misfolded proteins

Alzheimer’s Disease: Caused by which proteins that disrupt what?

Beta-amyloid plaques (outside neurons) block synaptic communication + Twisted fibers of tau protein (inside neurons) disrupt intracellular transport

Mutations linked to Alzheimer’s

• Presenilin

• ApoE

Presenilin → affects gamma-secretase (cutting long form of beta amyloid plaques → early onset AD
ApoE → protein involved in moving lipids, has 3 alleles

• presence of E4 allele = increased risk of late onset AD

Alzheimer’s Disease: Treatments

No cure; treatment = slowing progression; other than age, biggest risk factor = TBI; Keeping mind/body active = preventative

Dementia is defined as?

Progressive impairments to memory, thinking, and behavior (resulting from a neurological disorder) that affect the ability to perform everyday activities

Parkinson’s Disease: Caused by which proteins that disrupt what?

Lewy bodies = clumps of alpha-synclein protein (inside neurons) → interfere with dopaminergic synapses (block comms) → causes motor symptoms (tremors, muscles stiffness, balance and walking difficulty)

Parkinson’s Disease: gene mutations

• what happens normally

• what happens w/ mutation in alpha-synclein

• what happens w/ mutation in parkin

Usually: Parkin identifies misfolded protein and “tags” it with Ubiquitin, then Proteasome breaks down misfolded proteins

Alpha-synclein mutation = misfolded protein not recognized by parkin

Parkin mutation = Parkin doesn’t tag misfolded protein with ubiquitin

Parkinson’s Disease: Treatments

No cure

Drug treatments focus on L-DOPA (precursor of dopamine that crosses blood brain barrier and then turns into dopamine)

If that doesn’t work, then DBS targeting Globus Pallidus and Subthalamic nucleus to reduce abnormal activity in those regions

Huntingtin’s Disease: Caused by which proteins that disrupt what?

Mutation in huntingin gene = “long” version of the gene (<39 repeats) accumulate inside neurons → degeneration of neurons in caudate nucleus and putamen (basal ganglia) → motor symptoms = uncontrollable jerky movements

Huntington’s Disease: Treatment

No cure or efficient treatment

Antisense therapy: make antisense DNA bind to mRNA → blocks translation of mRNA into protein and breaks it down