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Effects of age on the glucoregulatory response following acute glucoprivation induced by 2-deoxyglucose (2DG) in the adrenal medulla of Sprague Dawley rats

Muda NA, Ramlan H, Damanhuri HA

Neuro Endocrinol. Lett., 2017 Jul;38(3):224-235.
PMID: 28759191

OBJECTIVES: Impairment in glucose homeostasis is one of the factors that may alter the feeding drive, hunger and satiety signals, which essential to maintain a sufficient level of energy for daily activities especially among the elderly. Adrenal medulla is one of the important organs that involves in glucose homeostasis through secretion of catecholamines. The catecholamines biosynthesis pathway utilizes various enzymes and protein kinases. The aims of this study are to investigate the effects of age on the biosynthetic pathway of catecholamines in adrenal medulla by determining the level of blood glucose and blood catecholamines, the gene and protein expression of biosynthetic catecholamine enzymes (TH, DBH and PNMT) as well as protein kinase substrates that involved in the phosphorylation of TH in 2DG-induced rats.
METHODS: Adrenal medulla from male Sprague Dawley rats at the age of 3-months (n=12) and 24-months (n=12) were further divided into two groups: 1) treatment group with 2DG to create glucoprivation condition and 2) the vehicle group which received normal saline as control.
RESULTS: The results showed that the level of glucose, adrenaline and noradrenaline were increased in response to acute glucoprivation conditions in both young and old rats. No age-related differences were found in the basal gene expression of the enzymes that involved in the catecholamines biosynthesis pathway. Interestingly the expressions of TH and DBH protein as well as the level of TH phosphorylation at Ser40, PKA, PKC and ERK1/2 substrates were higher in basal condition of the aged rats. However, contradicted findings were obtained in glucoprivic condition, which the protein expressions of DBH, pERK1/2 and substrates for pPKC were increased in young rats. Only substrate for pCDK was highly expressed in the old rats in the glucoprivic condition, while pPKC and pERK1/2 were decreased significantly. The results demonstrate that adrenal medulla of young and old rats are responsive to glucose deficit and capable to restore the blood glucose level by increasing the levels of blood catecholamines.
CONCLUSION: The present findings also suggest that, at least in rats, aging alters the protein expression of the biosynthetic catecholamine enzymes as well as protein kinase substrates that may attenuate the response to glucoprivation.
Hydralazine administration activates sympathetic preganglionic neurons whose activity mobilizes glucose and increases cardiovascular function

Parker LM, Damanhuri HA, Fletcher SP, Goodchild AK

Brain Res, 2015 Apr 16;1604:25-34.
PMID: 25662772 DOI: 10.1016/j.brainres.2015.01.049

Hypotensive drugs have been used to identify central neurons that mediate compensatory baroreceptor reflex responses. Such drugs also increase blood glucose. Our aim was to identify the neurochemical phenotypes of sympathetic preganglionic neurons (SPN) and adrenal chromaffin cells activated following hydralazine (HDZ; 10mg/kg) administration in rats, and utilize this and SPN target organ destination to ascribe their function as cardiovascular or glucose regulating. Blood glucose was measured and adrenal chromaffin cell activation was assessed using c-Fos immunoreactivity (-ir) and phosphorylation of tyrosine hydroxylase, respectively. The activation and neurochemical phenotype of SPN innervating the adrenal glands and celiac ganglia were determined using the retrograde tracer cholera toxin B subunit, in combination with in situ hybridization and immunohistochemistry. Blood glucose was elevated at multiple time points following HDZ administration but little evidence of chromaffin cell activation was seen suggesting non-adrenal mechanisms contribute to the sustained hyperglycemia. 16±0.1% of T4-T11 SPN contained c-Fos and of these: 24.3±1.4% projected to adrenal glands and 29±5.5% projected to celiac ganglia with the rest innervating other targets. 62.8±1.4% of SPN innervating adrenal glands were activated and 29.9±3.3% expressed PPE mRNA whereas 53.2±8.6% of SPN innervating celiac ganglia were activated and 31.2±8.8% expressed PPE mRNA. CART-ir SPN innervating each target were also activated and did not co-express PPE mRNA. Neurochemical coding reveals that HDZ administration activates both PPE+SPN, whose activity increase glucose mobilization causing hyperglycemia, as well as CART+SPN whose activity drive vasomotor responses mediated by baroreceptor unloading to raise vascular tone and heart rate.
Fulltext Perception of content and non-content expert facilitators of PBL according to students' performance levels

Ismail NA, Alias E, Arifin KT, Damanhuri MH, Karim NA, Aan GJ

Pak J Med Sci, 2015 Nov-Dec;31(6):1537-41.
PMID: 26870131 DOI: 10.12669/pjms.316.8691

Problem-based learning (PBL) is a student-centred learning system that involves multidisciplinary fields focused on problem solving. Facilitators of PBL are not necessarily content experts but little is known on how this concept has affected the outcomes of PBL sessions in learning Medical Biochemistry. We aimed to evaluate the impact of having the content expert as a facilitator in conducting PBL.
Behavioral Assessment and Blood Oxidative Status of Aging Sprague Dawley Rats through a Longitudinal Analysis

Achin NA, Kit TJ, Ngah WZW, Makpol S, Mazlan M, Hamezah HS, et al.

Curr Aging Sci, 2018;11(3):182-194.
PMID: 30338748 DOI: 10.2174/1874609811666181019141217

BACKGROUND: Cognitive frailty emerges as one of the threats to healthy aging. It is in continuum with advancing of age with uncertain indicator between pathological and physiological changes. Alterations in pathways associated with the aging process have been observed including oxidative stress, lipid metabolism, and inflammation. However, the exact mechanisms leading to cognitive decline are still unclear.
OBJECTIVE: This study was sought to assess the level of cognitive functions and linked with blood oxidative status during normal aging in rats.
METHODS: A longitudinal study using male Sprague Dawley rats was performed starting from the age of 14 months old to 27 months old. Cognitive functions tests such as open field, Morris water maze and object recognition were determined at the age of 14, 18, 23, and 27 months old and were compared with group 3 months old. Blood was collected from the orbital venous sinus and oxidative status was determined by measuring the level of DNA damage, lipid peroxidation, protein oxidation and antioxidant enzymes activity.
RESULTS: Aged rats showed declining exploratory behavior and increased in the level of anxiety as compared to the young rats. The level of DNA damage increased with increasing age. Interestingly, our study found that both levels of malondialdehyde and plasma carbonyl content decreased with age. In addition, the level of superoxide dismutase activity was significantly decreased with age whereas catalase activity was significantly increased from 18 months of age. However, no significant difference was found in glutathione peroxidase activity among all age groups.
CONCLUSION: The progressions of cognitive impairment in normal aging rats are linked to the increment in the level of DNA damage.
Fulltext Mucosal genetic immunization through microsphere-based oral carriers

Rosli R, Nograles N, Hanafi A, Nor Shamsudin M, Abdullah S

Hum Vaccin Immunother, 2013 Oct;9(10):2222-7.
PMID: 24051430 DOI: 10.4161/hv.25325

Polymeric carriers in the form of cellulose acetate phthalate (CAP) and alginate (ALG) microspheres were used for encapsulation of plasmid DNA for oral mucosal immunization. Access into the intestinal mucosa by pVAX1 eukaryotic expression plasmid vectors carrying gene-coding sequences, either for the cholera enterotoxin B subunit (ctxB) immunostimulatory antigen or the green fluorescent protein (GFP), delivered from both types of microsphere carriers were examined in orally immunized BALB/c mice. Demonstration of transgene protein expression and IgA antibody responses at local mucosal sites suggest immunological response to a potential oral DNA vaccine formulated within the microsphere carriers.
Cellulose acetate phthalate microencapsulation and delivery of plasmid DNA to the intestines

Hanafi A, Nograles N, Abdullah S, Shamsudin MN, Rosli R

J Pharm Sci, 2013 Feb;102(2):617-26.
PMID: 23192729 DOI: 10.1002/jps.23389

Cellulose acetate phthalate (CAP) microcapsules were formulated to deliver plasmid DNA (pDNA) to the intestines. The microcapsules were characterized and were found to have an average diameter of 44.33 ± 30.22 μm, and were observed to be spherical with smooth surface. The method to extract pDNA from CAP was modified to study the release profile of the pDNA. The encapsulated pDNA was found to be stable. Exposure to the acidic and basic pH conditions, which simulates the pH environment in the stomach and the intestines, showed that the release occurred in a stable manner in the former, whereas it was robust in the latter. The loading capacity and encapsulation efficiency of the microcapsules were low but the CAP recovery yield was high which indicates that the microcapsules were efficiently formed but the loading of pDNA can be improved. In vitro transfection study in 293FT cells showed that there was a significant percentage of green-fluorescent-protein-positive cells as a result of efficient transfection from CAP-encapsulated pDNA. Biodistribution studies in BALB/c mice indicate that DNA was released at the stomach and intestinal regions. CAP microcapsules loaded with pDNA, as described in this study, may be useful for potential gene delivery to the intestines for prophylactic or therapeutic measures for gastrointestinal diseases.