Psychology 3625 Cellular and Molecular Neuroscience Dr Darren Hannesson
Lecture 6 Cells of the nervous system Neurons Glia Other cell types Blood-brain barrier
Types of nervous system cells Neurons The main signaling units in the nervous system Humans have 100,000,000,000 Interconnections enable everything from basic reflexes to our highest cognitive functions Glial cells Historically have been thought to play primarily a supporting role Humans have 1,000,000,000,000 Several different kinds (astrocytes( astrocytes, oligodendroglia, Schwann cells) Cells of the immune system (microglia( microglia) Other cells Ependymal cells Endothelial cells Pericytes
Other types of cells Meninges Dura mater Arachnoid layer Subarachnoid space Pia mater
Other types of cells Meninges
Other types of cells Cerebroventricular system System of arachnoid space that surrounds brain and forms cavities in central part of brain and spinal cord Filled with cerebrospinal fluid (CSF)
Other types of cells Cerebroventricular system Purpose Contributes to homeostasis of the extracellular milieu in the CNS Buoys brain Cushions CNS
Other types of cells Ependymal cells Arise from ectoderm Macroglia? Cilia extend into lumen of ventricles
Other types of cells Ependymal cells Functions Production of CSF Choroid plexus
Other types of cells Ependymal cells Functions Production of CSF Circulation of CSF
Other types of cells Ependymal cells Functions Production of CSF Circulation of CSF Blood CSF barrier
Other types of cells Ependymal cells Functions Production of CSF Circulation of CSF Blood CSF barrier, CSF brain barrier
Other types of cells Blood-brain brain-barrier barrier (BBB)
Other types of cells Blood-brain brain-barrier barrier (BBB) The mechanisms that limit the movement of molecules between the blood and CNS What does the BBB achieve? Limits toxin entry to CNS Sequesters peripheral and central chemical signals
brain-barrier barrier (BBB) Why is it needed? Functional importance of CNS CNS exposure to blood Heavy reliance on chemical communication in CNS Limited ability for brain repair
How is the BBB achieved?
How is the BBB achieved? Endothelial cells Tight junctions have increased resistance Transcellular routes are reduced Fluid phase endocytosis Transcellular channels (fenestra( fenestra)
How is the BBB achieved? Endothelial cells Tight junctions have increased resistance
How is the BBB achieved? Endothelial cells Tight junctions have increased resistance
How is the BBB achieved? Endothelial cells Transcellular routes are reduced Fluid phase endocytosis
How is the BBB achieved? Endothelial cells Transcellular routes are reduced Fluid phase endocytosis is minimal Transcellular channels (fenestra)
How is the BBB achieved? Pericytes Similar to smooth muscle Regulate capillary wall tone
How is the BBB achieved? Basement membrane
How is the BBB achieved? Astroglia Endfeet almost completely surround the basement membrane on almost all capillaries in the brain
How is the BBB achieved? Astroglia Endfeet almost completely surround the basement membrane on almost all capillaries in the brain Why? Astroglia play an important role in inducing the unique endothelial cell characteristics of the BBB Evidence: Brain areas without a BBB, Pathological conditions, Cell culture studies
Astroglia induction of the BBB Evidence Brain areas without a BBB E.g., area postrema Absence of glial endfeet Absence of tight junctions
Astroglia induction of the BBB Evidence Brain areas without a BBB Pathological conditions
Astroglia induction of the BBB Evidence Brain areas without a BBB Pathological conditions Experimental studies
How do astroglia induce the BBB? Soluble factors camp RBE4 +camp +ACM
How do astroglia induce the BBB? Soluble factors camp,, GDNF
How do astroglia induce the BBB? Molecular changes γgtp
How do astroglia induce the BBB? Molecular changes γgtp TfR GLUT-1
What gets thru the BBB? lipid soluble molecules actively moved molecules
What gets thru the BBB? How?
Clinical importance of BBB Breakdown of BBB could play a role in nervous system disorders BBB is a critical consideration in drugs designed for CNS activity
Clinical importance of BBB Changes in BBB are seen in: Cerebral amyloid angiopathy - Alzheimer s Multiple sclerosis Brain tumours Traumatic brain injury Hypertension, Ischaemia, Stroke HIV-related dementia, Cerebral malaria, Bacterial meningitis Epilepsy Depression Schizophrenia
Clinical importance of BBB Multiple sclerosis
Clinical importance of BBB Causes of reduced BBB efficacy Structural changes
Clinical importance of BBB Causes of reduced BBB efficacy Chemical modulation
Clinical importance of BBB Causes of reduced BBB efficacy Chemical modulation Extracellular Intracellular
Clinical importance of BBB BBB is a critical consideration in drugs designed for CNS activity ty 3 options for access Lipid solubility Transport mediated Special delivery mechanisms
Clinical importance of BBB BBB is a critical consideration in drugs designed for CNS activity ty 3 options for access Lipid solubility
Clinical importance of BBB BBB is a critical consideration in drugs designed for CNS activity ty 3 options for access Lipid solubility Transport mediated
Clinical importance of BBB BBB is a critical consideration in drugs designed for CNS activity ty 3 options for access Lipid solubility Transport mediated Special delivery mechanisms
Clinical importance of BBB BBB is a critical consideration in drugs designed for CNS activity Special considerations in disease
Suggested readings Ballabh P, Braun A, Nedergaard M. The blood-brain brain barrier: an overview: structure, regulation, and clinical implications. Neurobiol Dis. 2004 Jun;16(1):1-13. 13.