Synaptic formation

Fig. 4.1 Hypothetical model of pathogenesis of pain in DSP. (1) Injury of peripheral nerve fibers due to multifocal inflammation and secreted macrophage activation products results in abnormal spontaneous activity of neighboring uninjured nociceptive fibers ( peripheral sensitization ). (2) Furthermore, the aberrant inflammatory response in DRG leads to alterations in neuronal sodium and calcium channel expression and ectopic impulse generation. (3) This results in central remodeling within the dorsal horn due to A-fiber sprouting and synaptic formation with pain fibers in lamina 11, and maintenance of neuropathic pain ( central sensitization ). Reproduced with permission from (Keswani et al. 2002)...

High concentrations (from 10"5 to 10"1 M) either quickly destroy the mechanism of biopotential generation or block the transmission in the synaptic formations, thus sharply decreasing the electrical activity of giant axons. However, the concentrations ranging from 10"4 to 10" 3 M are far from physiological and this makes the interpretation of this effect rather difficult. 

Changes in brain structure can occur in many different ways. For instance, neuronal death or disruptions in neuronal maturation (see also section 3.2), differentiation (see also section 3.7), migration, synaptic formation, glial and neurochemical development (see also section 3.4), can all have effects on brain structure. 

Most studies show that iodine deficiency and maternal—fetal hypothyroxinemia have negative effects on fetal neural maturation, dendritic arborization and synaptic formation. It also significantly delays axonal myelinization and gfio-genesis, which starts at the third trimester and accelerates in the postnatal period. Recent studies have clearly demonstrated the necessary role of maternal thyroxine in early neurogenesis (de Escobar et al., 2004 Bernal, 2005). 

Researchers have also studied the transplantation of ESNPCs into TBl models. Shindo et al. (2006) transplanted mouse ESNPCs into both mild and severe mouse TBl models. They observed better survival and differentiation of NPCs in the mild injury model compared to the severe injury model. Additional differences in synaptic formation and growth factor expression were also observed between the mild and severe injury models. 

Methylphenidate like cocaine largely acts by blocking reuptake of monoamines into the presynaptic terminal. Methylphenidate administration produces an increase in the steady-state (tonic) levels of monoamines within the synaptic cleft. Thus, DAT inhibitors, such as methylphenidate, increase extracellular levels of monoamines. In contrast, they decrease the concentrations of the monoamine metabolites that depend upon monoamine oxidase (MAO), that is, HVA, but not catecholamine-o-methyltransferase (COMT), because reuptake by the transporter is required for the formation of these metabolites. By stimulating presynaptic autoreceptors, methylphenidate induced increase in dopamine transmission can also reduce monoamine synthesis, inhibit monoamine neuron firing and reduce subsequent phasic dopamine release. 

Matsuoka M., Kaba H., Mori Y. and Ichikawa M. (1997). Synaptic plasticity in olfactory memory formation in female mice. Neurorep 8, 2501-2504. 

Figure 21.6 Time-lapse observation of synaptic acid crystal formation. The spray-droplet method forms very fine crystals inside and outside of the matrix drop (a-d), so that finer and more homogeneous crystals are generated (d) than those obtained by the droplet method (e-h). Observation with a scanning electron microscope of matrix crystals with the spray-droplet (i) and droplet methods (j). Reprinted with permission from Sugiura et al.7... 

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