Psychology 3625 Cellular and Molecular Neuroscience. Dr Darren Hannesson

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1 Psychology 3625 Cellular and Molecular Neuroscience Dr Darren Hannesson

2 Lecture 6 Cells of the nervous system Neurons Glia Other cell types Blood-brain barrier

3 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

4 Other types of cells Meninges Dura mater Arachnoid layer Subarachnoid space Pia mater

5 Other types of cells Meninges

6 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)

7 Other types of cells Cerebroventricular system Purpose Contributes to homeostasis of the extracellular milieu in the CNS Buoys brain Cushions CNS

8 Other types of cells Ependymal cells Arise from ectoderm Macroglia? Cilia extend into lumen of ventricles

9 Other types of cells Ependymal cells Functions Production of CSF Choroid plexus

10 Other types of cells Ependymal cells Functions Production of CSF Circulation of CSF

11 Other types of cells Ependymal cells Functions Production of CSF Circulation of CSF Blood CSF barrier

12 Other types of cells Ependymal cells Functions Production of CSF Circulation of CSF Blood CSF barrier, CSF brain barrier

13 Other types of cells Blood-brain brain-barrier barrier (BBB)

14 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

15 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

16 How is the BBB achieved?

17 How is the BBB achieved? Endothelial cells Tight junctions have increased resistance Transcellular routes are reduced Fluid phase endocytosis Transcellular channels (fenestra( fenestra)

18 How is the BBB achieved? Endothelial cells Tight junctions have increased resistance

19 How is the BBB achieved? Endothelial cells Tight junctions have increased resistance

20 How is the BBB achieved? Endothelial cells Transcellular routes are reduced Fluid phase endocytosis

21 How is the BBB achieved? Endothelial cells Transcellular routes are reduced Fluid phase endocytosis is minimal Transcellular channels (fenestra)

22 How is the BBB achieved? Pericytes Similar to smooth muscle Regulate capillary wall tone

23 How is the BBB achieved? Basement membrane

24 How is the BBB achieved? Astroglia Endfeet almost completely surround the basement membrane on almost all capillaries in the brain

25 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

26 Astroglia induction of the BBB Evidence Brain areas without a BBB E.g., area postrema Absence of glial endfeet Absence of tight junctions

27 Astroglia induction of the BBB Evidence Brain areas without a BBB Pathological conditions

28 Astroglia induction of the BBB Evidence Brain areas without a BBB Pathological conditions Experimental studies

29 How do astroglia induce the BBB? Soluble factors camp RBE4 +camp +ACM

30 How do astroglia induce the BBB? Soluble factors camp,, GDNF

31 How do astroglia induce the BBB? Molecular changes γgtp

32 How do astroglia induce the BBB? Molecular changes γgtp TfR GLUT-1

33 What gets thru the BBB? lipid soluble molecules actively moved molecules

34 What gets thru the BBB? How?

35 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

36 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

37 Clinical importance of BBB Multiple sclerosis

38 Clinical importance of BBB Causes of reduced BBB efficacy Structural changes

39 Clinical importance of BBB Causes of reduced BBB efficacy Chemical modulation

40 Clinical importance of BBB Causes of reduced BBB efficacy Chemical modulation Extracellular Intracellular

41 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

42 Clinical importance of BBB BBB is a critical consideration in drugs designed for CNS activity ty 3 options for access Lipid solubility

43 Clinical importance of BBB BBB is a critical consideration in drugs designed for CNS activity ty 3 options for access Lipid solubility Transport mediated

44 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

45 Clinical importance of BBB BBB is a critical consideration in drugs designed for CNS activity Special considerations in disease

46 Suggested readings Ballabh P, Braun A, Nedergaard M. The blood-brain brain barrier: an overview: structure, regulation, and clinical implications. Neurobiol Dis Jun;16(1):

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