The Role of Leptin in the Brain for Catecholamine (TH) Neurons, Serotonin (5HT) Neurons and Orexin Neurons
CHAPTER II: LITERATURE REVIEW
Leptin is a hormone that plays a crucial role in regulation of food intake and in energy homeostasis (1-3). The hormone was initially identified in mutant mice displaying extreme obesity and feeding excessively. A few decades later, it was revealed that the mutant mice had inadequate proper leptin signalling which were attributed to a mutation in either the hormone (ob/ob) or its analogous receptor. Leptin is synthesised from the adipose tissue in proportion to the quantity of adipose tissue present ...view middle of the document...
The neuronal populations of LepRB are plenty within the midbrain, comprising of the ventral tegmental area, the periaqueductal gray (PAG) and the dorsal raphe (DR). However, the hypothalamus is comprised of the largest volume of the LepRb neurons, which are well disseminated within the dorsomedial hypothalamus, the ventromedial (VMH nuclei) and the lateral hypothalamic area (LHA) (6-9).
Upon the discovery of LepRb, medical scientists have devoted much attention into investigating and creating an understanding on how leptin acts. Elmquist et al. observed a considerable volume of LepRb neurons in the lateral hypothalamic area in the year 1996 (10). In the past years, numerous reports have discussed the functioning of leptin through lepRb, but it role in the lateral hypothalamic area had not been made clear. The rest of this literature review scrutinizes the neuronal populations with a special focus on the role of leptin in the brain for tyrosine hydroxylase (a catecholamine), serotonin (5HT) neurons and orexin neurons.
2.2 Tyrosine hydroxylase
Tyrosine hydroxylase (TH) is an enzyme that catalyses the rate-limiting phase in the biogenesis of the catecholamine (norepinephrine, epinephrine, and dopamine) (11). Catecholamine is a group of organic compounds that are involved in various physiological processes, including energy homeostasis and have an effect on the cardiovascular functioning by increasing heart rate and blood pressure (12). The catecholaminergic system rises from the main catecholimergic cell collections found in the upper brainstem, including locus coeruleus, ventral tagmental area and sustancianigra (13).
A number of past studies have focused on the role and the distribution of TH in the brain (13-16). Benavides‐Piccione and DeFelipe evaluated the distribution of TH immunoreactive cortical interneurons which are a type of interneuron commonly found in human neocortex. The researchers claimed that the interneurons are more prevalent in the human neocortex in comparison to other organisms and have a role in cortical circuits (13).
TH functioning is dependent on a broad range of regulatory mechanisms. This regulation can be categorised into two main groups; a short term mechanism (involves regulation of TH activity) and a long term mechanism (involves control of gene expression) (17). The short term regulation takes place at the posttranscriptional level. The main activities in this phase include regulation of TH phosphorylation, which is an activity that activates the enzyme. The enzyme is also activated by various types of protein kinases, including protein kinase C (PKC) family members. On the other hand, long term regulation consists of enzyme stability, translational regulation and has an effect on ribonucleic acid (RNA) stability after gene transcription (18-22).
There are reports documenting that various transcription factors bond to the 5′-flanking sequences of the tyrosine hydroxylase gene and can result in activation of...