Neonatal pyridoxine administration long lastingly accelerates cortical spreading depression in male rats, without affecting anxiety-like behavior

ABSTRACT

Objectives: Pyridoxine plays a key role in the development of the human nervous system. Several reports suggest that administration of high doses of pyridoxine can be helpful in improving disturbances such as anxiety and pyridoxine-dependent epilepsy, although it has also been associated with a proconvulsive action. In this study, we investigated in developing rats the effects of repeated administration of various doses of pyridoxine on anxiety-like behavior and the brain excitability-related phenomenon known as cortical spreading depression (CSD).

Methods: From postnatal day (P) 7 to P27, Wistar rat pups received per gavage pyridoxine hydrochloride (1 mg/kg/day, or 5 mg/kg/day, or 10 mg/kg/day). On P60-70, the animals were tested in the elevated plus maze (EPM) to evaluate anxiety-like behavior. On P71-80, we recorded the CSD (4-hour recording session).

Results: Compared with naïve (gavage-free) and saline-treated controls, pyridoxine-treated groups displayed a significant (p < 0.001) increase in CSD propagation velocity and amplitude of the CSD negative direct-current (DC)-shift, and a decrease in the CSD DC-shift duration. These effects were long-lasting and dose-dependent. In the EPM, no significant pyridoxine-associated effect was observed.

Discussion: Our data demonstrate a novel action of pyridoxine on an electrical activity-related phenomenon (CSD) in the developing brain, confirming the hypothesis that the chronic treatment with pyridoxine early in life modulates CSD. Data on CSD propagation suggest that pyridoxine at a high dose might act as a prooxidant agent in the developing brain, a hypothesis that deserves further testing.

KEYWORDS:

• Anxiety-like behavior
• brain development
• cortical spreading depression
• nutritional supplements
• pyridoxine
• neurotransmitters
• redox imbalance

Acknowledgements

This work was financially supported by Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq no. 445101/2014-8), Instituto Nacional de Ciência e Tecnologia em Excitoxicidade e Neuroprotecao’—Edital INCT/MCT/CNPq), and Capes (Edital 043/2013 Ciencias Do Mar II and BEX2036/15-0, Finance Code 001). RCA Guedes is research fellow from CNPq (No. 303636/2014-9).

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico: [grant number CNPq no. 445101/2014-8 and 303636/2014-9]; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior: [grant number 043/2013 Ciências Do Mar II and BEX 2036/15-0. Finance Code 001]; INCT/MCT/CNPq (Excitoxicidade e Neuroprotecao) [grant number 465671/2014-4].

Notes on contributors

Kelly Rayanne Gondim-Silva

Kelly Rayanne Gondim-Silva has graduated in Nutrition Sciences in 2012; she got the title of specialist in sport-nutrition in 2016; she got the Master course in Biochemistry and Physiology at Universidade Federal de Pernambuco (finished in 2019). She is currently member of the technical staff from Instituto Federal do Sertão in Salgueiro City, Pernambuco State, Brazil.

Joselma M. da-Silva

Joselma M. da-Silva has graduated in Pedagogics and Biological Sciences (2011); she got the Master course in Biochemistry and Physiology at Universidade Federal de Pernambuco (finished in 2019). She is currently member of the technical staff from Secretaria de Saúde, Municipal Administration of Surubim City, Pernambuco State, Brazil.

Laís A. V. de Souza

Laís A. V. de Souza is undergraduate student at the School of Nutrition Sciences, at Universidade Federal de Pernambuco, Recife, Brazil.

Rubem C. A. Guedes

Rubem C. A. Guedes has graduated in Human Medicine at the Medical School (Universidade Federal de Pernambuco, Brazil); Master in Biophisics (Universidade Federal do Rio de Janeiro, Brazil); Doctoral course in Human Medicine (area: Neurobiology) at the University of Göttingen, Germany. He is currently Full Professor for Nutrition and Neurophysiology at Department of Nutrition, Universidade Federal de Pernambuco, Recife, Brazil.