Otak dan Neurotransmiter

Hadi Sarosa

Alzheimer’s Disease

• Clinical (1901) – Cognitive disturbance

– Disorientation

– Delusions

– Aphasia

– Behavior dyscontrol

• Post mortem (1906) – Presenile dementia

• Striking generalized cortical atrophy

• Unique neuropathological changes

• Publication (1911) – Histology

• Neurofibrillary tangles (NFT)

• Neuritic plaques

Alois Alzhemer (1901), clinical case Auguste D, ♀, ages : 51 years

Matthews B.R. & Miller B.L. (2009) Alzheimer’s disease. In The Behavioral Neurology of Dementia. Miller B.L. & Boeve B.F. (ed). Cambridge University Press. pp. 56-73.

chromosome 19

Evolusi

Situasi saat ini

Gen Pengalaman

Organisme saat ini

Perilaku saat ini

Interaksi Faktor Genetik dan Pengalaman

• Tyron (1994) : Selective-breeding (maze-bright dan maze-dull)

• Asbjörn Fölling (1934): Phenylketonuria (PKU)

– Defisiensi fenilalamin hidroksilase mengkonversi fenilalamin menjadi tyrosin, bahan untuk disintesis menjadi dopamin

Behaviour (tingkah laku)

Menggambarkan fungsi seluruh sistem saraf

– Kegiatan motorik bawah sadar

– Reflek bawah sadar

– Emosi, kesenangan, ketakutan, cemas, sex

– Atur fungsi vegetatif

Kardiovaskuler,suhu tubuh,

Hormonal, metabolisma, berat badan

Pusat kenyang, pusat haus.

– Fungsi luhur (moral) : Fungsi kognitif

Cognitive function • Cognitive function, an intellectual process by

which one becomes aware of, perceives, or comprehends ideas. It involves all aspects of perception, thinking, reasoning, and remembering.

Mosby's Medical Dictionary, 8th edition. © 2009, Elsevier.

• Cognition: means of acquiring and processing

information about our selves and our world

COGNITIVE DOMAINS :

• Memory (acquiring, retaining, and retrieving new information)

• Attention and concentration (particularly divided attention)

• Information processing (dealing with information gathered by the five senses)

• Executive functions (planning and prioritizing) • Visuospatial functions (visual perception and

constructional abilities) • Verbal fluency (word-finding)

• Each hemisphere of the cortex can further be divided into four lobes:

• Occipital - visual processing

• Parietal - movement, orientation, calculation, recognition

• Temporal - sound and speech processing, aspects of memory

• Frontal - thinking, conceptualisation, planning.

Cortical Functional Networks

Dorsomedial Prefrontal

Cortex

Ventromedial Prefrontal

Cortex

Inferior Parietal Lobus

Lateral Temporal

Cortex

Posteromedial Cortex : Retrosplenial Cortex

Posterior Cingulate Cortex Precuneus

Hippocampus Parahippocampal

Cortex

Glutamatergic excitatory input

Frontal Lobe

• Conscientiousness • Judgments • How we initiate activity in response to our environment. • Controls our emotional response. • Controls our expressive language. • Assigns meaning to the words we choose (abstract thought) • Attention span • Involves word associations (language planning) • Memory for habits and motor activities (short term memory) • Motor cortex—Voluntary movement • Impulse control • Perseverance

Frontal Lobe Deficit—Problems • Loss of simple movement of various body parts (Paralysis). • Inability to plan a sequence of complex movements needed to

complete multi-stepped tasks, such as making coffee (Sequencing).

• Loss of spontaneity in interacting with others. • Loss of flexibility in thinking. • Persistence of a single thought (Perseveration). • Inability to focus on task (Attending). • Mood changes (Emotionally Labile). • Changes in social behavior. • Changes in personality. • Difficulty with problem solving. • Inablility to express language (Broca's Aphasia).

Parietal Lobe Function

• Location for visual attention.

• Location for touch perception.

• Goal directed voluntary movements.

• Manipulation of objects.

• Integration of different senses that allows for understanding a single concept.

Parietal Lobe—Problems resulting from deficit

• Inability to attend to more than one object at a time. • Inability to name an object (Anomia). • Inability to locate the words for writing (Agraphia). • Problems with reading (Alexia). • Difficulty with drawing objects. • Difficulty in distinguishing left from right. • Difficulty with doing mathematics (Dyscalculia). • Lack of awareness of certain body parts and/or

surrounding space (Apraxia) that leads to difficulties in self-care.

• Inability to focus visual attention. • Difficulties with eye and hand coordination.

Temporal Lobe Function

• Hearing ability

• Memory acquisition

• Some visual perceptions

• Categorization of objects.

Temporal Lobe Deficits—Problems • Difficulty in recognizing faces (Prosopagnosia). • Difficulty in understanding spoken words

(Wernicke's Aphasia). • Disturbance with selective attention to what we

see and hear. • Difficulty with identification of, and verbalization

about objects. • Short-term memory loss. • Interference with long-term memory • Increased or decreased interest in sexual behavior. • Inability to catagorize objects (Catagorization). • Right lobe damage can cause persistant talking. • Increased aggressive behavior.

Occipital Lobe Function

• Vision

Occipital Lobe Deficits--Problems

• Defects in vision (Visual Field Cuts). • Difficulty with locating objects in environment. • Difficulty with identifying colors (Color Agnosia). • Production of hallucinations • Visual illusions - inaccurately seeing objects. • Word blindness - inability to recognize words. • Difficulty in recognizing drawn objects. • Inability to recognize movement of an object

(Movement Agnosia). • Difficulties with reading and writing.

Amygdala,

Hippocampus dan

nuclei septal

Fungsi

• Pengaturan olfactori

• Respon autonom

• Perilaku sexual

• Emosi : marah, takut

• Motivasi

Komunikasi Neuron di Otak

A. IMPULS LISTRIK

B. ZAT KIMIA : NEUROTRANSMITTER

1. Asetil kolin

2. Asam amino

Gama-aminobutyric acid (GABA)

Glutamat

Aspartat

Glycine

3. Monoamine

Dopamin

Histamin

NE

Serotonin

4. Neuropeptide

Somatostatin

Endorphin

Enkaphalin

substance P

Otak : listrik & Neurotransmitter

Potensial membran

Neurotransmitter

Neurotransmiter

Molekul Kecil Konvensional

Asam Amino

Glutamat eksitatorik

Aspartat

Glisin

Gammaaminobutyric acid (GABA) Inhibitorik

Mono Amine Catecholamines ( Tirosin)

dopamin

epinefrin

norepinefrin

Indolalamin (Tryptophan) serotonin

Asetilkolin Asetilkolin

Molekul Kecil tak Konvensional

Gas gas yang dapat larut

Oksida Nitrit

Karbon monosida

Endokanabinoida Anandamida

Molekul Besar Neuropeptide

Peptida pituitaria

Peptida hipotalamik

Peptida opiat

Neurotransmiter Sistem ekstrapiramidal

Neurotransmitter

Nigrostriatal pathway Substantia Nigra to Striatum . Motor control . Death of neurons in this pathway can result in Parkinson's Disease

Tuberoinfundibular pathway Hypothalamus to Pituitary gland . Hormonal regulation . Maternal behavior (nurturing) . Pregnancy . Sensory processes

Mesolimbic and Mesocortical pathways Ventral Tegmental Area to Nucleus Accumbens, Amygdala & Hippocampus, and Prefrontal Cortex . Memory . Motivation and emotional response . Reward and desire . Addiction . Can cause hallucinations and schizophrenia if not functioning properly

The Dopamine Pathways

Raphe Nuclei

The Serotonin Pathways

Dihasilkan oleh nuclei Raphe Dipengaruhi oleh obat : Amphetamin, alkohol, cocaine Berperan penting dalam proses di otak : pengaturan temperatur, mood, lapar, nyeri dan tidur

Problems with the serotonin pathway can cause obsessive-compulsive disorder, anxiety disorders, and depression. Most of the drugs used to treat depression today work by increasing serotonin

levels in the brain.

Glutamate and GABA (gamma-aminobutyric

acid) are the brain's major "workhorse"

neurotransmitters. Over half of all brain synapses

release glutamate, and 30-40% of all brain synapses

release GABA.

Alcohol decreases glutamate activity

Caffeine inhibits GABA release

PCP "angel dust" increases glutamate activity

Caffeine increases glutamate activity

Alcohol increases GABA activity

Tranquilizers increase GABA activity

Sedatif-Hipnotik dan Ansiolitik

• Golongan Barbiturat

– meningkatkan respon GABA

– membuka kanal ion Cl- meski tanpa GABA

• Golongan Benzodiazepin

Anti Depresan

1. Serotonin Spesific Reuptake inhibitor (SSRI)

misal : Fluoxetin

2. Heterosiklik

mengeblok reuptake serotonin dan norepinefrin, dan sebagai antagonis reseptor muskarinik. sehingga kadar serotonin dan NE tinggi (misal : desipramin, imipramin)

3. Serotonin Norephinefrin Reuptake Inhibitor (SNRI)

Depresi : Kadar dopamin, serotonin dan NE menurun

Anti Depresan

4. MAO inhibitor

menghambat MAO menghancurkan serotonin, dopamin dan NE (misal : isokarboksamid)

5. Lain-lain antagonis reseptor alfa 2

presinaptik sekresi serotonin dan NE meningkat (misal : Mirtazapiin)

Antipsikotik (neuroleptik)

Typical neuroleptik Untuk mengobati gejala positif

dengan menurunkan dopamin

Mekanisme :

mengeblok reseptor dopamin, kolinergik muskarinik, alfa adrenergik dan H-1 histaminergik

Contoh :

Klorpromasin, Haloperidol (potensi besar namun efek samping paling besar yaitu parkinson), Acetofenasin

Atypical, 5-HT DA Antagonist Untuk mengobati gejala postif & negatif :

menghambat reseptor dopamin dan serotonin

Mekanisme :

antagonis serotonin-dopamin, mengeblok reseptor kolinergik muskarinik, alfa-1 adrenergik dan H-1 histaminergik

Contoh :

Clozapine, Quetiapine

Psikotik : Kadar Dopamin & Serotonin >>

Parkinson

• Ganglia Basalis : serabut dopaminergik << asetyl cholin >>

1. Pengganti dopamin (terapi utama)

a. levodopa : prekursor metabolik dopamin

b. karbidopa : inhibitor dekarboksilase dopamin -> menurunkan metabolisme levodopa -> kadar levodopa meningkat

c. tolkapon : inhibitor COMT (Catechol-O-Methyl-transferase) sehingga levodopa bisa hidup lebih lama (waktu paro lebih panjang) dan kadarnya dalam darah meningkat

2. Agonis reseptor dopamin (misal : bromokriptin, pergolid, pramipexole)

3. Antikolinergik (misal : triheksifenidil, benzotropin)

NEUROPLASTISITAS OTAK

Kemampuan Otak untuk berubah dan mengubah

strukturnya sebagai

Respon terhadap rangsangan dari luar (lingkungan)

Menunjukkan bahwa situasi dan lingkungan yang tepat

Dapat memberikan pengaruh kuat terhadap perubahan otak

Keadaan lingkungan yang berkaitan

dengan Neuroplastisitas Otak

1.Kegiatan Fisik (Voluntary Gross Motor)

2.Pembelajaran baru, menantang dan penuh

makna

3.Kesulitan yang logis (tidak bikin kacau)

4.Stresor yang dapat dikelola dengan baik

5.Dukungan sosial (rumah dan komunitas)

6.Nutrisi yang baik

7.Waktu yang mencukupi