Module 3, lecture 5 Flashcards
why is nervous tissue unlike any other kind of tissue
limited regeneration in CNS
Neurons characteristics
- Mostly post-mitotic cells (will never divide again, not mitotically active)
-Neurons have a unique shape among cells (polarized and specialized)
-Neurons must maintain connections with each other to communicate, some involve very long distances! (challenging to find target when its far away)
- Information is stored in these connections long-term
Glial scar tissue often replaces neurons after injury (repair) after neuronal/axonal loss
➔ Limited potential for regeneration and repair, particularly in the brain
Physical injuries and neurodegenerative diseases often bring about…
irreversible damage and loss (to neurons/axons) of function to CNS
In mammals, such loss of function is due to the inability of adult mammalian CNS neurons to regenerate (repair/regeneration decreases are we age, especially in CNS, prenatally less deleterious than postnatally)
A limited degree of CNS self-repair exists early in development; however, the ability to spontaneously regenerate is dramatically reduced after parturition
Injuries Associated with the Nervous System
Acute insults:
Trauma, hypoxia (low O2 levels), ischemia (low blood supply due to global ischemia, ischemic stroke)
Injuries Associated with the Nervous System
Neurodegenerative diseases (NDS):
Genetic basis, Adult-onset, e.g. Alzheimer’s (AD), Parkinson’s (PD), and Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS)
Regeneration vs. Repair
Regeneration: perfect structural and functional replacement, full recovery
Repair: not perfect repair, you see scar tissue
Barriers to Brain regeneration and Repair
- Neuronal death: differences in sensitivity (cell death)/survival varies among cell types and injury location and severity
- Transcriptional programs active in developing neurons are downregulated postnatally (and are not easily re-activated by injury) limiting the capacity of regenerative potential of mature CNS neurons (regrowth programs that exist during prenatal development are down-regulated post-natally. Only in CNS (hard time activating these programs) not PNS.
- Different Activation of glial cells and immune responses that inhibit axonal growth (different in CNS and PNS)
- Adult stem cells are present in limited numbers and regions (SC niches in brain: SVZ and SGZ; in olfactory bulb) CNS only has 2 regions w/SCs and very limited in number
- In NDs, presence of an early ‘silent’ phase (hard to detect); later – neurodegeneration is widespread (hard to diagnose, diagnose too late)
Nervous System Responses after Injury - Different strategies to restore function after injury:
Functional reorganization without regeneration/repair (applies to acute and genetic based injury)
Axonal regeneration = axon regrowth (after injury) and the subsequent innervation of target regions resulting in recovery function (mostly possible in PNS)
Differences between PNS vs CNS (e.g. lower motor neurons vs. upper motor neurons) differences are based on environment cells are in (ex: motor neurons found in CNS and PNS - knee jerk reflex)
Glial scar
Neurogenesis (die from toxins/drugs)
Functional Reorganization – Example 1
Reorganization of existing circuits after focal damage as a result of retention of experience-dependent plasticity
1ry (primary) motor cortex
→ Activation of ‘silent’ connections followed by changes in synaptic efficacy among those connections
altered cortical activity patterns are correlated with functional recovery after a focal stroke. (green area: increase in activity and recovery of function over time)
Functional Reorganization – Example 2
Reorganization of existing circuits after focal damage as a result of retention of experience-dependent plasticity
epidural electrical stimulation for spinal cord injury.
→ Recruitment of intact connections And activation of reflex circuit via Epidural electrical stimulation (EES)
connections between descending axons (regulate reflex circuits) and motor neurons and interneurons distal to the lesion are diminished or completely lost after injury
-epidural electrical stimulation device allows for modulation of pattern, intact axons could be recruited to make the whole circuit functional again
Axon regrowth
When peripheral axons are severed, the neuron, whether in a peripheral ganglion or in the CNS, regenerates the distal portion of the axon
Neuronal Repair
Injury to CNS neurons causes loss of neurons and connections; scar tissue replaces area once occupied by neurons.
Glial scar (looks like target): reactive glia (core: immune cells + ECM + fibroblasts), glia = scar periphery, core: inside
Neuronal Replacement
NSCs -> neuroblasts -> new neurons.
(e.g. replacement of olfactory receptor neurons (ORNs) in the olfactory bulb (OB) from basal SCs)
when exposed to different toxins, infections cause death of these neurons, neurons are replaced by stem cells found in the basal layer of the epithelium
tissue regeneration is usually complete within 1–2 months after injury
from: viral infection, chronic rhinosinusitis (CRS), head trauma, inflammation
Potential Benefits from Adult neurogenesis
and example
Neural plasticity
Memory (eg. spatial patterning)
Cognition
Affective behavior
Eg: neuroblasts born in the SVZ migrate singly into the OB, where they may differentiate into GABAergic interneurons - Migratory path: rostral migratory stream (RMS). The difference is that this is during the adult stage so just a few/single pairs of neuroblasts are migrating and will reach the OB, will give rise to GABAergic neurons
Potential Dysfunctions from Adult neurogenesis
Neurological disorders (eg: Alzeimers, epilepsy)
Psychiatric disorders (eg: depression, anxiety)
Brain tumors
