Banca de QUALIFICAÇÃO: ANA CAROLLINY FERNANDES FARIA

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : ANA CAROLLINY FERNANDES FARIA
DATE: 26/08/2021
TIME: 13:30
LOCAL: Videoconferência
TITLE:

INVOLVEMENT OF MELATONIN IN THE AUTISTIC PHENOTYPE: THE ROLE OF Na,K-ATPase

Autism (ASD) is a developmental disorder that causes changes even in early childhood in areas of communication, social interaction and learning, as well as in the ability to adapt. There are numerous genetic variations that can be considered as possible causes of ASD, but none of them are responsible for more than 1% of cases and many of these environmental factors are associated with melatonin (MEL) deficiency, a hormone synthesized by the pineal gland during the period. dark at night. The chance of developing ASD is higher in newborns who have a late onset of breastfeeding or who are bottle-feeding, as there is an increased risk of having MEL deficiency and a greater likelihood of developing ASD. The activity of Na,K-ATPase (NKA) is reduced in these individuals, it is  involved in the maintenance of the Na+ and K+ gradient across the cell membrane, it is essential for the conduction of the nerve impulse and its malfunction may results in a reduction learning and memory capacity. In the present study, it was evaluated through biochemical parameters, whether the absence of maternal MEL (pinealectomized rats) induces the development of TEA in pups and whether exogenous MEL replacement in pinealectomized rats is able to prevent or delay the appearance of TEA in puppies . Biochemical tests were performed on the cerebellum of offspring of wistar rats after the 4th week of life. Previously, the rats were divided into 5 groups: (1) pinealectomized rats with melatonin supplementation (MEL group); (2) pinealectomized rats without melatonin supplementation (PTX group); (3) female rats who underwent pinealectomy surgical procedure without removing the pineal (SHAM group); (4) rats injected with sodium valproate on the 13th gestational day (VPA group) and (5) rats that did not undergo any procedures (CONTROL group). The activities of the enzymes Na, K-ATPase, Acetylcholinesterase, reduced Glutathione (GSH), Lipid peroxidation and H2O2 produced were analyzed, as well as the expressions of the isoforms α1, α2 and α3 of Na, K-ATPase. Our results showed that there was a significant reduction in α2/α3 activity in the MEL group, however there were no significant differences in the other tests, not even in the expression of NKA isoforms. Thus, our results show that MEL has an action on NKA, the α3 subunit is mainly expressed in the pineal gland and α2 is also in large amounts in the brain, opening the possibility for further studies to be carried out to investigate this interaction and if there is any alteration in the individual with ASD or other neurodegenerative diseases.

 

KEY WORDS:

Autism, Melatonin, Na,K-ATPase, Oxidative stress, Cerebellum.

PAGES: 39
BIG AREA: Ciências da Saúde
AREA: Farmácia
SUMMARY:

Autism (ASD) is a developmental disorder that causes changes even in early childhood in areas of communication, social interaction and learning, as well as in the ability to adapt. There are numerous genetic variations that can be considered as possible causes of ASD, but none of them are responsible for more than 1% of cases and many of these environmental factors are associated with melatonin (MEL) deficiency, a hormone synthesized by the pineal gland during the period. dark at night. The chance of developing ASD is higher in newborns who have a late onset of breastfeeding or who are bottle-feeding, as there is an increased risk of having MEL deficiency and a greater likelihood of developing ASD. The activity of Na,K-ATPase (NKA) is reduced in these individuals, it is  involved in the maintenance of the Na+ and K+ gradient across the cell membrane, it is essential for the conduction of the nerve impulse and its malfunction may results in a reduction learning and memory capacity. In the present study, it was evaluated through biochemical parameters, whether the absence of maternal MEL (pinealectomized rats) induces the development of TEA in pups and whether exogenous MEL replacement in pinealectomized rats is able to prevent or delay the appearance of TEA in puppies . Biochemical tests were performed on the cerebellum of offspring of wistar rats after the 4th week of life. Previously, the rats were divided into 5 groups: (1) pinealectomized rats with melatonin supplementation (MEL group); (2) pinealectomized rats without melatonin supplementation (PTX group); (3) female rats who underwent pinealectomy surgical procedure without removing the pineal (SHAM group); (4) rats injected with sodium valproate on the 13th gestational day (VPA group) and (5) rats that did not undergo any procedures (CONTROL group). The activities of the enzymes Na, K-ATPase, Acetylcholinesterase, reduced Glutathione (GSH), Lipid peroxidation and H2O2 produced were analyzed, as well as the expressions of the isoforms α1, α2 and α3 of Na, K-ATPase. Our results showed that there was a significant reduction in α2/α3 activity in the MEL group, however there were no significant differences in the other tests, not even in the expression of NKA isoforms. Thus, our results show that MEL has an action on NKA, the α3 subunit is mainly expressed in the pineal gland and α2 is also in large amounts in the brain, opening the possibility for further studies to be carried out to investigate this interaction and if there is any alteration in the individual with ASD or other neurodegenerative diseases.

BANKING MEMBERS:
Externo à Instituição - ISRAEL JOSE PEREIRA GARCIA
Presidente - 1526269 - LEANDRO AUGUSTO DE OLIVEIRA BARBOSA
Externa ao Programa - 1106384 - LUCIANA ESTEFANI DRUMOND DE CARVALHO