Brain pathways

Responses in the dopamine system are more complex (see chapter by Balfour, this volume). Repeated nicotine injections resulted in enhanced extracellular DA levels in the NAc (Benwell and Balfour 1992, 1997), but not in the striatum (Benwell and Balfour 1997). Analysis of the precise placement of dialysis probes has revealed differential responses to drugs of abuse, including nicotine, between the NAc core (ventral striatum) and shell (Di Chiara 2002 Balfour 2004 Wonnacott et al. 2005 see chapter by Balfour, this volume). Moreover, the sensitised neurotransmitter responses observed in the hippocampus and NAc were markedly attenuated if rats received a constant infusion of a low level of nicotine (Benwell and Balfour 1997). Thus, transient peaks of nicotine appear capable of sensitising some brain pathways with respect to catecholamine release, but the responses may be mitigated by lower sustained plasma concentrations, possibly due to desensitisation. The extent that presynaptic nAChRs contribute to this process in vivo is unclear presynaptic a7 nAChRs on glutamatergic afferents to the VTA merit attention as potential mediators of sensitisation (see Sect. 2.2.2). 

Norepinephrine A neurotransmitter that is important in certain brain pathways and in the terminal synapses of the sympathetic nervous system (SYN noradrenaline). 

Pietrowsky, R., Struben, C., Molle, M., Fehm, H. L., and Born, J. (1966), Brain potential changes after intranasal vs. intravenous administration of vasopressin Evidence for a direct nose-to-brain pathway for peptide effects in humans, Biol. Psychiatry, 39, 332-340. 

Cocaine (3)has a completely different structure and, as we shall see later, its mechanism of action is also somewhat different from the structurally simpler (l)and (2). Nevertheless, all of these natural prototype CNS stimulants have the common action of exerting powerful effects on brain pathways that utilize dopamine as the neurotransmitter. 

The numerical diversity of Na channel genes and their variable expression patterns increase the probabihty that the anticipated channel subunit mutations will generate multiple CNS excitability profiles finked to distinct clinical seizure types. Each of these selective excitability increases in specific axonal pathways may act to synchronize large neuronal populations by synaptic or non-synaptic mechanisms. This review considers the anatomical aspects of Na channel involvement in epileptogenesis, namely, how the site of expression of the Na channel gene, both within the neuron and within specific brain pathways, acts as an important phenotypic determinant of the disorder. 

Phenethylamines are only one of many classes of chemicals which alter the activity levels of specific brain tissue. What sets phenethylamine compounds apart, is that some of the brain pathways whose activity they alter, affect uniquely human functions, such as cognition, the religious or aesthetic sentiments, the self-concept, fantasy, childhood memories, and the unconscious human psyche. 

Because different receptor types have different physical distributions, different spectrums of binding affinities and activities will result in the alteration of activity patterns of different regions of the brain. Perhaps the most surprising implication of the phenethylamine data is that there is evidently a very high diversity of receptor types for these compounds in humans, thus allowing subtle and selective pharmacological manipulation of very many specific brain pathways. 

Figure 6.4. Scheme illustrating the absorption, translocation, and excretory pathways of nanostructures within the body. The solid arrows indicate confirmed routes, whereas dashed arrows indicate potential routes. BBB refers to the blood-brain barrier and CSBB is the cerebrospinal-brain barrier. Adapted from Oberdorster, G. Nanoparticles (NP) and the Brain Pathways of Translocations and Effects, International conference on Nanotechnology, Cincinnati, Ohio, Dec. 7, 2006. May be accessed online at http // www.uc.edu/NOEHS/pdf/Thursday/Copy%20of%20Cincinnati%20NIOSoberdorsterH.pdf. 

Stockhorst, U., and Pietrowsky, R. (2004) Olfactory perception, communication, and the nose-to-brain pathway. Physiol. Behav. 83, 3-11... 

The chromaffin cells of the adrenal medulla may be considered to be modified sympathetic neurons that are able to synthesize E from NE by /V-methylation. In this case the amine is Hberated into the circulation, where it exerts effects similar to those of NE in addition, E exhibits effects different from those of NE, such as relaxation of lung muscle (hence its use in asthma). Small amounts of E are also found in the central nervous system, particularly in the brain stem where it may be involved in blood pressure regulation. DA, the precursor of NE, has biological activity in peripheral tissues such as the kidney, and serves as a neurotransmitter in several important pathways in the brain (1,2). 

Fig. 2. Biosynthetic pathway for epinephrine, norepinephrine, and dopamine. The enzymes cataly2ing the reaction are (1) tyrosine hydroxylase (TH), tetrahydrobiopterin and O2 are also involved (2) dopa decarboxylase (DDC) with pyridoxal phosphate (3) dopamine-P-oxidase (DBH) with ascorbate, O2 in the adrenal medulla, brain, and peripheral nerves and (4) phenethanolamine A/-methyltransferase (PNMT) with. Cadenosylmethionine in the adrenal...

The primary fate of acetyl CoA under normal metabolic conditions is degradation in the citric acid cycle to yield C02. When the body is stressed by prolonged starvation, however, acetyl CoA is converted into compounds called ketone bodies, which can be used by the brain as a temporary fuel. Fill in the missing information indicated by the four question marks in the following biochemical pathway for the synthesis of ketone bodies from acetyl CoA ... 

Masters CL Beyreuther K (2006). Alzheimer s centennial legacy prospects for rational therapeutic intervention targeting the AB amyloid pathway. Brain 129 2823-2839... 

The cytokine leptin is secreted by adipocytes (fat cells) in proportion to the size of the adipose dq>ot and circulates via the bloodstream to the brain, where it ultimately affects feeding behavior, endocrine systems including reproductive function and, at least in rodents, energy expenditure. The major effect of Lqrtin is on the hy-pothalamous, where it suppresses appetite and hence food intake. Leptin exerts its effects via binding to the leptin receptor in the brain (specifically in the hypothalamus), which activates the JAK-STAT Pathway. 

---