DL-Aspartic acid administration improves semen quality in rabbit bucks.

Recently, D-aspartic acid (d-Asp) has been suggested as being involved in mechanisms regulating reproduction activity in animals and human. In this study we analyzed the effects of DL-Asp oral administration on sperm production in the rabbit. Bucks from 60, bred in a genetic centre and used for semen production, were divided in 2 subgroups of 6 individuals. The treated group was fed with a concentrate containing DL-Asp which assured a daily administration of 1.3g dl-Asp/head; the control group was fed with the same concentrate without DL-Asp. The treatment was carried out for 2wk and animals were monitored weekly, from 1wk before the start of the treatment to 3wk after the end of the treatment. Through the experimental period there were no significant variations in semen volume between the two groups. A significant increase in both sperm concentration and kinetic parameters, i.e., the overall percentage of motile spermatozoa, the average path velocity, the percentage of progressively motile spermatozoa, etc., was found in the supplemented group. L-Asp values in blood serum and seminal plasma did not vary through the experimental period. D-Asp concentration in blood serum increased more than 4-fold than baseline (P<0.01) at the end of the treatment and was maintained at higher than baseline values for up to 3wk after the end of the treatment. D-Asp concentration in seminal plasma was higher than in blood serum before the start of the treatment (13.7+/-1.6nM vs 3.5+/-3.3nM; P<0.01) which suggests an elective storage of D-Asp in the male genital tract. Baseline values of d-Asp concentration in seminal plasma significantly increased following treatment and were back to initial values 1wk after the end of the treatment. In conclusion, DL-Asp administration improved sperm quality in bucks and the high D-Asp content in seminal plasma suggests a primary role for this D-amino acid in regulatory mechanisms of reproductive activity.

Differential prepuberal handling modifies behaviour and excitatory amino acids in the forebrain of the Naples High-Excitability rats.

Naples High-Excitability (NHE) rats model the mesocortical variant of Attention-Deficit Hyperactivity Disorder (ADHD). Recently, a high level of excitatory amino acids (EAA) has been found in the forebrain of NHE rats. The aim of this study was to verify the effect of postnatal stimulation in prepuberal rats on forebrain EAA. Thus, prepuberal NHE and Naples Random Bred (NRB) control rats were daily handled (PS) or they were left undisturbed throughout (NO-PS). One hour after the last stimulation, PS and NO-PS rats were exposed to a spatial novelty in a Làt-maze and one day later to a non-reinforced Olton maze. In both tests the horizontal (HA) and vertical (frequency - VA and duration of rearing - RD) components of behaviour indexed activity and non-selective attention (NSA). Moreover, in the Olton maze the position of the number of arms visited before first repetition (FE) and to criterion (NVTC), indexed selective spatial attention (SSA). Amino acids were detected by HPLC in prefrontal cortex (PFC), striatum (STR), hippocampus (HPC) and hypothalamus (HYP). Results indicate that (i) in the Làt-maze, only for HA, NO-PS NHE rats were more active than PS, (ii) in the Olton maze NO-PS rats of both lines showed shorter rearing durations than PS, (iii) EAA level was higher in NHE than in NRB rats and (iv) NO-PS vs. PS treatment increased level of EAA across the forebrain in both rat lines. In contrast in NHE NO-PS rats L-glutamate (L-Glu) decreased in HYP and L-aspartate (L-Asp) decreased in HPC. In conclusion, postnatal stimulation in prepuberal rats significantly affects forebrain excitatory amino acids and behaviour in NHE line. Thus EAA are modulated by genetic determinants and environmental (epigenetic) factors.

Excitatory amino acids in the forebrain of the Naples high-excitability rats: neurochemical and behavioural effects of subchronic D-aspartate and its diethyl ester prodrug.

The excitatory amino acids (EAA) L-glutamate (L-Glu), L-aspartate (L-Asp) and D-aspartate (D-Asp) are thought to play a neurotransmitter/neuromodulator role in neuronal communications. Recently, a high level of EAA L-Glu, D- and L-Asp isomers has been found in the forebrain of Naples high-excitability (NHE) rat line that models the mesocortical variant of Attention-Deficit Hyperactivity Disorder (ADHD). The aim of this study was to assess the functions of D-Asp using two forms, i.e. free D-Asp or D-Asp diethyl ester (DEE) as prodrug, on brain and behaviour. Thus, prepuberal rats were given, for two weeks daily, an i.p. injection of D-Asp or DEE or vehicle. Then rats were exposed to two spatial novelties i.e. Làt and radial Olton maze. Behaviour was monitored for indices of activity, non-selective attention (NSA), selective spatial attention (SSA) and emotional reactivity. L-Glu and D- and L-Asp were detected by HPLC in cognitive and non-cognitive brain areas such as prefrontal cortex, striatum, hippocampus and hypothalamus. Results indicate that subchronic D-Asp or DEE (i) reduced EAA levels in the NHE and increased it in the random-bred controls (NRB) rats, (ii) in the Làt-maze D-Asp increased horizontal activity in NHE but DEE decreased it in NRB rats, (iii) in the Olton maze D-Asp and DEE decreased vertical activity in NHE and NRB rats respectively, (iv) D-Asp impaired attention only in NRB decreasing number of arms visited before first repetition. Therefore, data demonstrate differential effects of prepuberal subchronic D-Asp and DEE that may be related to different basal EAA levels in NHE and NRB rats.

Elevated forebrain excitatory L-glutamate, L-aspartate and D-aspartate in the Naples high-excitability rats.

The Naples high-excitability (NHE) rats are thought to model the mesocortical variant of attention-deficit hyperactivity disorder (ADHD). The aim of this study was to investigate forebrain level of L-glutamate, L-aspartate and D-aspartate, in NHE vs. Naples random bred (NRB) control rats. Thus, prepuberal NHE and NRB rats were daily handled in the 5th and 6th week of postnatal life. Then rats were exposed to two spatial novelties i.e. a Làt and a Olton maze for 10 min. Amino acids were detected by HPLC in the prefrontal cortex (PFC), striatum (STR), hippocampus (HPC) and hypothalamus (HYP). Results indicate that all amino acids were higher in NHE than in NRB rats. This, in turn, may explain the behavioural hyperactivity and attention deficit of this animal model of ADHD.

Reproductive implication of D-aspartic acid in human pre-ovulatory follicular fluid.

BACKGROUND: In the present study, we report that D-aspartic acid (D-Asp) occurs in human ovarian follicular fluid and that a relationship may exist between the concentration of this amino acid and oocyte quality. METHODS: Samples of pre-ovulatory follicle fluid were obtained from 20 patients undergoing an IVF programme. The concentration of D-Asp was measured by using specific high-performance liquid chromatography (HPLC) combined with a d-aspartate oxidase. RESULTS: D-Asp occurs in human follicular fluid at a mean concentration of 14.98 +/- 4.51 nmol/ml. A significant difference in the content of this amino acid in the follicular fluid in relation to patient's age exists. In younger women aged 22-34 years (group A), D-Asp was found at a concentration of 19.11 +/- 1.91 nmol/ml, whereas in patients aged 35-40 years (group B), it decreased to 10.86 +/- 1.22 nmol/ml (P < 0.01). In addition, this amino acid was linked to oocyte quality; a relationship exists between D-Asp follicular concentration and the percentage of good quality metaphase II oocytes (P < 0.01), as well as the fertilization rate. CONCLUSIONS: In human follicular fluid, D-Asp is present at a relatively higher concentration in younger women than in older patients and there appears to be a relationship between the concentration of d-Asp and fertility outcome parameters. These findings suggest that follicular D-Asp concentration may be considered as an alternative or additional biochemical marker for oocyte quality in patients undergoing IVF programmes.