Brain neurons

T No A PKA Brain (neuron), adrenal (medulla) Neurotransmission, synaptic plasticity, LTP, memory,circadian rhythm... 

A (Hex A) catalyzing the biodegradation of gangliosides. Accumulation of gangliosides in lysosomes primarily affects brain neurons. In the early onset form of the disease, children become blind, deaf, and unable to swallow. Children die usually before the age of three. A late onset form ofthe disease occurs in young adults and is usually nonfatal. 

The neuropeptides are peptides acting as neurotransmitters. Some form families such as the tachykinin family with substance P, neurokinin A and neurokinin B, which consist of 11 or 12 amino acids and possess the common carboxy-terminal sequence Phe-X-Gly-Leu-Met-CONH2. Substance P is a transmitter of primary afferent nociceptive neurones. The opioid peptide family is characterized by the C-terminal sequence Tyr-Gly-Gly-Phe-X. Its numerous members are transmitters in many brain neurones. Neuropeptide Y (NPY), with 36 amino acids, is a transmitter (with noradrenaline and ATP) of postganglionic sympathetic neurones. 

DAT is predominantly expressed by dopaminergic brain neurons, NET by noradrenergic neurons in the central and peripheral nervous system, and SERT is restricted to the axons of serotonergic neurons, which originate in the raphe nuclei and innervate numerous higher brain regions therefore SERT is widely distributed in the brain. Outside the brain, 5HT transport can be measured on non-neuronal cells (e.g. platelets, lympho-blastoid cells and smooth muscle cells) most of the 5HT appearing in the circulation is taken up by platelets. 

The action of 5-HT on brain neuronal systems is complex depending on the neurons involved, it can induce inhibition or excitation. Experiments with iontophoretic application of LSD to neurons have shown that 5-HT-induced excitation is invariably blocked by LSD, whereas LSD mimics inhibition at sites where 5-HT exerts an inhibiting effect (Aghajanian et al. 1987 Martin and Sloane 1986). Tryptamine itself is found in all major regions of... 

Ellis R, Langford D, MasUah E (2007) HIV and antiretroviral therapy in the brain neuronal injury and repair. Nat Rev Neurosci 8(1) 33 4... 

Dahlstrom, A., and Fuxe, K. Evidence for the existence of monoamine containing neurons in the central nervous system. 1. Demonstration of monoamines in cell bodies of brain neurons. Acta Physiol Scand (Suppl 232) 62 1-55, 1964. 

Majumdar, S. Mallick, B. N. (2005). Cytomorphometric changes in rat brain neurons after rapid eye movement sleep deprivation. Neuroscience 135,... 

Lin J. S., Hou Y., Jouvet M. (1996). Potential brain neuronal targets for amphetamine-, methylphenidate-, and modafinil-induced wakefulness, evidenced by c-fos immunocytochemistry in the cat. Proc. Natl. Acad. Sci. USA 93, 14128-33. 

The binary threshold activation function was used in early attempts to create ANNs because of a perceived parallel between this function and the way that neurons operate in the brain. Neurons require a certain level of activation before they will "fire," otherwise they are quiescent. A TLU functions in the same way. 

In animal studies, high levels of cortisol have been shown to induce (increase) the activity of the enzyme tryptophan 2,3-dioxygenase in the liver, thereby decreasing the bioavailability of tryptophan to the brain. It is interesting to note that low acute doses of a number of different antidepressants inhibit the activity of this enzyme and, as a result, increase brain tryptophan concentrations, thus stimulating 5-HT synthesis (Badawy and Evans, 1982). In this way a link between the two key monoamine neurotransmitters and the hormone may be seen namely, reduced brain NA activity leads to decreased inhibition of the HPA axis, while increased levels of cortisol reduce 5-HT activity in the brain. Activation of the HPA axis has also been shown to result in tissue atrophy, in particular of the limbic system s hippocampus, and a reduction in the levels of neurotrophic factors responsible for the maintenance and optimal function of brain neurons (Manji et al., 2001). In conclusion, manipulation of the HPA axis (Nemeroff, 2002) and stimulation of neurotrophic factor activity (Manji et al., 2001) might open up new avenues for the treatment of affective disorders. 

Epilepsy A group of neurological disorders characterised by abnormal electrical activity of brain neurons (seizures). 

Yamagata, K., Andreasson, K. I., Kaufmann, W. E., Barnes, C. A. and Worley, P. F. Expression of a mitogen-inducible cyclooxygenase in brain neurons regulation by synaptic activity and glucocorticoids. Neuron 11 371-386,1993. 

Cui, Z. Z., Wang, H., Tan, Y. et al. Inducible and reversible NR1 knockout reveals crucial role of the NMDA receptor in preserving remote memories in the brain. Neuron 41 781-793, 2004. 

Zinc is important to the normal functioning of the central nervous system (CNS). At low concentrations, zinc protects mammalian brain neurons by blocking N-methyl-D-aspartate receptor-mediated toxicity. At high concentrations, zinc is a potent, rapidly acting neurotoxicant in the mammalian brain, as judged by zinc-induced neuronal injury of in vitro mature cortical cell cultures (Choi et al. 1988). Increased brain levels of zinc are associated with Pick s disease in certain strains of rodents with inherited epileptic seizures. Intravenous injection of zinc in rats with genetically inherited epilepsy produces seizures a similar response occurs with intracranial injection of zinc in rabbits with inherited audiogenic seizures (Choi et al. 1988). 

Increased production of IL-6 following exposure to Pb has been demonstrated by several investigators [59, 67-70], Since IL-6 is a proinflammatory cytokine, increased production due to Pb exposure may influence many different tissues. Dylatov and Lawrence [68] provided evidence that Pb, IL-6 and LPS can combine to exert a significant impact on the permeability of the blood brain barrier as well as the properties of brain neurons and endothelial cells. Another proinflammatory cytokine, IL-ip, has been reported to increase following exposure to Pb [71], It seems probable that enhanced production of both IL-ip and IL-6 would increase the potential for local tissue inflammation. 

Striibing C, Krapininsky G, Krapivinsky L, Clapham DE 2001 TRPC1 and TRPC5 form a novel cation channel in mammalian brain. Neuron 29 645-655 Trepakova ES, Csutora P, Hunton DL, Marchase RB, Cohen RA, Bolotina VM 2000 Calcium influx factor directly activates store-operated cation channels in vascular smooth muscle cells. J Biol Chem 275 26158-26163... 

Alzheimer s Disease The vaccine being tested contains a small protein called jS-amyloid (AjS). This protein forms abnormal deposits, or plaques, in the brains of people with Alzheimer s disease. Researchers believe that Kji deposition causes loss of mental function by killing the brain neurons. The strategy of Aji vaccination is to stimulate the immune system to clean up plaques and prevent further A deposits. Although preclinical and Phase I studies showed the potential of the vaccine, the Phase II clinical trial was halted because 15 of 360 patients developed severe brain inflammation. Further studies showed that the A did generate the desired... 

Using the knowledge that rabies virus can spread into the brain neurons, scientists mimic its delivery system. A short, 29 amino acid peptide chain is derived from the rabies virus glycoprotein (RVG). The RVG binds to the acetylcholine receptor on the neurons and the endothelium cells of the blood-brain barrier. Through this interaction, transvascular delivery is enabled. 

The drug in this case, a siRNA, was coupled to the RVG peptide and successfully delivered to the neurons in mice. This work opens up the possibility of using the RVG as delivery tools for drugs designed for interaction with brain neurons. 

Oyama Y, Chikahisa L, Ueha T, Kanemaru K, Noda K. (1996). Ginkgo biioba extract protects brain neurons against oxidative stress induced by hydrogen peroxide. Brain Res. 712(2) 349-52. 

Oyama Y, Fuchs PA, Katayama N, Noda K. (1994). Myricetin and quercetin, the flavonoid constituents of Ginkgo biioba extract, greatiy reduce oxidative metaboiism in both resting and Ca(2+)-loaded brain neurons. Brain Res. 635(1-2) 125-29. 

Lesioning of the terminal nerve system in hamsters disrupts mating behavior (Demski and Northcutt, 1983 Wirsig and Leonard, 1985). The terminal nerve is probably the sole source of all brain neurons containing gonadotropinreleasing hormone (Schwanzel-Fukuda and Pfaff, 1989). 

Epilepsy is a chronic brain disease of diverse etiology it is characterized by recurrent paroxysmal episodes of uncontrolled excitation of brain neurons. Involving larger or smaller parts of the brain, the electrical discharge is evident in the electroencephalogram (EEG) as synchronized rhythmic activity and manifests itself in motor, sensory, psychic, and vegetative (visceral) phenomena Because both the affected brain region and the cause of abnormal excitability may differ, epileptic seizures can take many forms. Erom a pharmaco-therapeutic viewpoint, these may be classified as ... 

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