Otak dan Neurotransmiter

Hadi Sarosa

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

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

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

chromosome
19

Evolusi

Gen

Pengalaman

Organisme saat ini

Situasi saat ini

Perilaku saat ini

Interaksi Faktor Genetik dan

Pengalaman
Tyron (1994) : Selective-breeding (maze-bright
dan maze-dull)
Asbjrn Flling (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

Inferior
Parietal
Lobus
Dorsomedial
Prefrontal
Cortex

Posteromedial Cortex :
Retrosplenial Cortex
Posterior Cingulate Cortex
Precuneus

Ventromedial
Prefrontal
Cortex

Lateral
Temporal
Cortex

Glutamatergic excitatory input

Hippocampus
Parahippocampal
Cortex

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 cortexVoluntary movement
Impulse control
Perseverance

Frontal Lobe DeficitProblems

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 LobeProblems 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 DeficitsProblems

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
Vision

Function

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.
B.

IMPULS LISTRIK
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
Glutamat
Asam Amino

Aspartat
Glisin
Gammaaminobutyric acid (GABA)

Molekul Kecil
Konvensional

Inhibitorik

dopamin
Mono Amine

Catecholamines ( Tirosin)

Asetilkolin
Gas gas yang dapat
Molekul Kecil tak larut
Konvensional
Endokanabinoida

Asetilkolin
Oksida Nitrit
Karbon monosida

Anandamida
Peptida pituitaria

Neuropeptide

epinefrin
norepinefrin

Indolalamin (Tryptophan)

Molekul Besar

eksitatorik

Peptida hipotalamik
Peptida opiat

serotonin

Neurotransmiter
Sistem ekstrapiramidal

Neurotransmitter

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

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

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

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

Raphe Nuclei

Problems with the serotonin pathway can cause obsessivecompulsive 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 3040% of all brain synapses
release GABA.

Alcohol
decreases
glutamate
activity

PCP
"angel
dust"
increases
glutamate
activity

Caffeine
inhibits
GABA
release

Caffeine
increases
glutamate
activity

Alcohol
increases
GABA
activity

Tranquilize
rs increase
GABA
activity

Sedatif-Hipnotik dan Ansiolitik

Golongan Barbiturat
meningkatkan respon
GABA
membuka kanal ion Clmeski tanpa GABA

Golongan
Benzodiazepin

Anti Depresan
Depresi : Kadar dopamin, serotonin dan NE menurun
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)

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)
Psikotik : Kadar Dopamin & Serotonin >>
Typical neuroleptik

Atypical, 5-HT DA Antagonist

Untuk mengobati gejala positif

Untuk mengobati gejala postif & negatif :
dengan menurunkan dopamin
menghambat reseptor dopamin dan
serotonin
Mekanisme :
Mekanisme :
mengeblok reseptor dopamin,
kolinergik muskarinik, alfa adrenergik
antagonis serotonin-dopamin, mengeblok
dan H-1 histaminergik
reseptor kolinergik muskarinik, alfa-1
adrenergik dan H-1 histaminergik
Contoh :
Contoh :
Klorpromasin, Haloperidol (potensi
besar namun efek samping paling
Clozapine, Quetiapine
besar yaitu parkinson), Acetofenasin

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