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PubMed1990

Interstitial thermoradiotherapy of brain tumors: preliminary results of a phase I clinical trial.

A Phase I clinical trial has been initiated to determine the feasibility, tolerance, and toxicity of interstitial thermoradiotherapy in the treatment of high-grade supratentorial brain gliomas. Hyperthermia was delivered by means of thermally-regulating ferromagnetic implants afterloaded into stereotactically placed plastic catheters. Heat treatments were given immediately before interstitial irradiation; in addition, five patients received a second heat treatment at the completion of brachytherapy. The desired target temperature for the 60-minute hyperthermia session was between 42 degrees C and 45 degrees C. Following hyperthermia, the catheters were afterloaded with Ir-192, which delivered a variable radiation dose of 14-50 Gy depending on the clinical situation. Interstitial irradiation was supplemented with external beam radiotherapy (40-41.4 Gy) in patients with previously untreated tumors. A total of 14 patients (4 males, 10 females) have been treated to date on this protocol. Eleven of the patients had a diagnosis of glioblastoma multiforme, whereas three had anaplastic astrocytoma. The mean implant volume was 61.5 cm3 (range: 9-119 cm3); the median number of interstitial treatment catheters implanted was 19 (range: 7-33). Continuous temperature monitoring was performed by means of multisensor thermocouple probes inserted in the center as well as in the periphery of the tumor. Of the 175 monitored intratumoral points, 83 (47%) had time-averaged mean temperatures of greater than 42 degrees C, and only 12 sensors (7%) exceeded a temperature of 45 degrees C. Among the 19 heat treatments attempted, there have been four minor acute toxicities, all of which resolved with conservative medical management and one major complication resulting in the demise of a patient. These preliminary results indicate that ferromagnetic implants offer a promising new approach to treating brain tumors with hyperthermia.

Adult↗
PubMed2004

Technical improvement in permanent seed implantation: a two-stage brachytherapy system. Description and comparison with current technique.

PURPOSE: Permanent seed implantation by available techniques has modest limitations. A new, two-stage needle design and technique is described and evaluated in comparison to a conventional permanent seed technique. METHODS AND MATERIALS: The technique involves placing a stylet and sleeve initially into the all target coordinates prior to seed placement similar to temporary seed technique. The second stage involves consecutively removing the stylet from each sleeve and inserting a clear, plastic needle containing preloaded seeds into the sleeve and implanting the seeds. Fifty-six (125)I patients were treated with the two-stage technique. Comparisons were made with a cohort of 71 patients implanted using a conventional technique at the Seattle Prostate Institute. Prostate movement, surgical time, catheterization rate, and DVH postop dosimetry were analyzed. RESULTS: After an initial learning curve, the two-stage technique had surgical times similar to conventional techniques. Cephalad movement of 3-10 mm was noted in 4 (8%) patients vs. 71 (100%) patients with our conventional technique. Of the 6 (10%) patients who required Foley catheterization, 3 (5%) did so for 1 day and 3 (5%) did so for less than 3 weeks. Day 1 CT scan based dosimetry was calculated on all patients. The V100 ranged from 80-100% with a median of 92.5%. For primary cases, the V100 (<85%) was 14% for the conventional vs. 7% for the two-stage technique. No two-stage patient had a V100 <80%. The V100 values for the two-stage and conventional techniques demonstrated a possible advantage with the two-stage technique (mean V100 92.6% vs. 90.7%, [p=0.051]). The D90 for the two-stage technique ranged from 123-190 Gy with a median of 151.5 Gy for implant only and a median of 127 Gy for boost cases. The D90 values for the two-stage patients were slightly but not statistically better than the conventional technique (p=0.232). Thirty-one percent of conventional technique patients had a D90 <140 Gy vs. 22% for two-stage technique. CONCLUSION: This new two-stage brachytherapy technique may offer some advantages over conventional techniques including: simple and improved needle loading verification, less complicated and better visualization of needle placement, improved stabilization of the gland, and more consistent postoperative dosimetry.

Brachytherapy↗
PubMed2003

Deep brain stimulation for Parkinson's disease.

Deep brain stimulation at high frequency was first used in 1997 to replace thalamotomy in treating the characteristic tremor of Parkinson's disease, and has subsequently been applied to the pallidum and the subthalamic nucleus. The subthalamic nucleus is a key node in the functional control of motor activity in the basal ganglia. Its inhibition suppresses symptoms in animal models of Parkinson's disease, and high frequency chronic stimulation does the same in human patients. Acute and long-term results after deep brain stimulation show a dramatic and stable improvement of a patient's clinical condition, which mimics the effects of levodopa treatment. The mechanism of action may involve a functional disruption of the abnormal neural messages associated with the disease. Long-term changes, neural plasticity and neural protection might be induced in the network. Similar effects of stimulation and lesioning have led to the extension of this technique for other targets and diseases.

Electric Stimulation Therapy↗
PubMedDate not supplied

A target glitter study.

A target study was conducted using four different pre-selected types of commercial glitter particles. Recipient areas in the general environment around San Diego, California were tested. Glitter particles were recovered using double-sided tape affixed to square plastic Petri dishes. White light microscopy was the only search/identification method used. Additionally, a test was performed of the transferability of cosmetic glitter. Glitter particles were found to readily transfer. Of a total of 48 tape lifts from the general environment, 23 were found to contain at least one glitter particle. But due to the wide variety of glitter particles in terms of colour, shape, size, and surface morphology, the likelihood of transfer of one or more specific target particles was small.

Journal Article↗
PubMed1998

Measurement of tryptophan hydroxylase mRNA levels by competitive RT-PCR.

Tryptophan hydroxylase (TPH) is the rate limiting enzyme in serotonin biosynthesis [D.G. Grahame-Smith, Tryptophan hydroxylation in brain, Biochem. Biophys. Res. Commun. 16 (1964) 586-592 [19]]. As such, the TPH gene is a likely target for modulation of serotonergic function, which has been associated with several psychiatric disorders [E.C. Azmitia, P.M. Whitaker-Azmitia, Awakening the sleeping giant: anatomy and plasticity of the brain serotonergic system, J. Clin. Psychiatry 52 (12, Suppl.) (1991) 4-16 [1]; R.P. Hart, R. Yang, L.A. Riley., T.L. Green, Post-transcriptional control of tryptophan hydroxylase gene expression in rat brain stem and pineal gland, Mol. Cell. Neurosci. 2 (1991) 71-77 [20]; M.J. Owens, C.B. Numeroff, Role of serotonin in the pathophysiology of depression: focus on the serotonin transporter, Clin. Chem. 40 (1994) 288-295 [24]]. Unfortunately, it has been technically difficult to measure TPH mRNA levels in central serotonergic neurons due to its low levels. For example, detection with ribonuclease protection assays requires pooling of 5-10 dissected brainstems [M.C. Darmon, B. Guibert, V. Leviel, M. Ehret, M. Maitre, J. Mallet, Sequence of two mRNAs encoding active rat tryptophan hydroxylase, J. Neurochem. 51 (1988) 312-316 [15]; B.L. Jacobs, E.C. Azmitia, Structure and function of the brain serotonin system, Physiol. Rev. 72 (1992) 165-229 [21]]. This protocol describes the use of competitive RT-PCR to measure TPH mRNA levels from rat brain. First described in 1988, competitive RT-PCR has become an accepted method of measuring RNA abundance [M. Clementi, S. Menzo, P. Bagnarelli, A. Manzin, A. Valenza, P.E. Varaldo, Quantitative PCR and RT-PCR in virology, PCR Methods Appl. 2 (1994) 191-196 [12]; N.C.P. Cross, Quantitative PCR techniques and applications, Br. J. Haematol. 89 (1995) 693-697 [14]; K.P. Foley, M.W. Leonard, J.D. Engel, Quantitation of RNA using the polymerase chain reaction, Trends Genet. 9 (1993) 380-385 [17]; P.D. Siebert, J.W. Larrick, Competitive PCR, Nature 359 (1992) 558 [27]]. Competitive RT-PCR uses co-amplification with a known quantity of an in vitro transcribed RNA which amplifies using the same primers and thus competes for reactants with the product of interest. As the two products amplify with the same efficiency, the relative abundance of the two amplification products remains constant, and thus can be used to determine initial tissue TPH mRNA levels [G. Gilliland, S. Perrin, K. Blanchard, H.F. Bunn, Analysis of cytokine mRNA and DNA: detection and quantitation by competitive polymerase chain reaction, Proc. Natl. Acad. Sci. U.S.A. 87 (1990) 2725-2729 [18]; A.M. Wang, M. V. Doyle, D.F. Mark, Quantitation of mRNA by the polymerase chain reaction, Proc. Natl. Acad. Sci. U.S.A. 86 (1989) 9717-9721 [31]]. We first demonstrate equivalent results between RNA slot blots and competitive RT-PCR using the CA77 thyroid C cell line [M.S. Clark, A. F. Russo, Tissue-specific glucocorticoid regulation of tryptophan hydroxylase mRNA levels, Mol. Brain Res. 48 (1997) 346-354 [9]]. We then describe the use of competitive RT-PCR to measure TPH mRNA levels in RNA isolated from rat brain poly-A+ RNA.

Animals↗
PubMed2001

Expression and functional significance of VE-cadherin in aggressive human melanoma cells: role in vasculogenic mimicry.

We recently have introduced the term vasculogenic mimicry to describe the unique ability of aggressive melanoma tumor cells to form tubular structures and patterned networks in three-dimensional culture, which "mimics" embryonic vasculogenic networks formed by differentiating endothelial cells. In the current study, we address the biological significance of several endothelial-associated molecules (revealed by microarray analysis) with respect to expression and function in highly aggressive and poorly aggressive human cutaneous melanoma cell lines (established from the same patient). In a comparative analysis, CD31 was not expressed by any of the melanoma cell lines, whereas TIE-1 (tyrosine kinase with Ig and epidermal growth factor homology domains-1) was strongly expressed in the highly aggressive tumor cells with a low level of expression in one of the poorly aggressive cell lines. Vascular endothelial (VE)-cadherin was exclusively expressed by highly aggressive melanoma cells and was undetectable in the poorly aggressive tumor cells, suggesting the possibility of a vasculogenic switch. Down-regulation of VE-cadherin expression in the aggressive melanoma cells abrogated their ability to form vasculogenic networks and directly tested the hypothesis that VE-cadherin is critical in melanoma vasculogenic mimicry. These results highlight the plasticity of aggressive melanoma cells and call into question their possible genetic reversion to an embryonic phenotype. This finding could pose a significant clinical challenge in targeting tumor cells that may masquerade as circulating endothelial cells or other embryonic-like stem cells.

Antigens, CD↗
PubMed2004

Development and validation of chromatographic methods for the identification and quantitation of organic compounds leached from a laminated polyolefin material.

Chromatographic methods for the identification of organic compounds leached from a plastic material used in solution containers in the pharmaceutical industry are described. Based on a set of compounds identified in extracts of a multilayered polyolefin film, targeted leachables are delineated for accumulation assessments, and methods to perform target quantitation are developed and validated.

Journal Article↗
PubMed2004

Olfactometric and rhinomanometric outcomes in post-menopausal women treated with hormone therapy: a prospective study.

BACKGROUND: The aim of this prospective study was to evaluate the effects of hormone therapy (HT) on olfactory sensitivity in post-menopausal women. METHODS: Forty-six naturally post-menopausal women underwent rhinomanometric and olfactometric measurements to compare nasal airflow resistance values and olfactometric thresholds during the eighth month of HT treatment with baseline levels prior to starting HT. Eighteen women used an oral HT regimen, and twenty-eight women used transdermal patch HT. RESULTS: Rhinomanometric values during HT were statistically differ from those at baseline (P < 0.001). Olfactometric threshold data indicated a higher sensitivity during the HT treatment than at baseline (P < 0.001). Finally, no statistically significant difference was observed among women using oral or patch HT administration on rhinomanometric and olfactometric values. CONCLUSIONS: Our study demonstrates that 8 months of treatment with estrogen and progestogens in HT preparations has an effect on nasal airflow resistance and the olfactory thresholds to odours. We believe that estrogens could influence neuronal plasticity, and the neuronal conduction time into the olfactory system. Our findings confirm that gonadal steroids such as estrogen have an influence on non-genital targets; this relationship might have a beneficial impact on sensorineural communication and emotional behaviour.

Administration, Oral↗
PubMed2000

Physiology and pathophysiology of alpha-synuclein. Cell culture and transgenic animal models based on a Parkinson's disease-associated protein.

The 15-20 kDa synuclein (SYN) phosphoproteins are abundantly expressed in nervous tissue. Members of the family include alpha- and beta-SYN, and the more distantly related gamma-SYN and synoretin. SYN genes have been identified in Torpedo, canary, and several mammalian species, indicating an evolutionary conserved role. Expression of alpha-SYN was found to be modulated in situations of neuronal remodeling, namely, songbird learning and after target ablation of dopaminergic striatonigral neurons in the rat. The presynaptic localization of alpha-SYN is further supportive of a direct physiological role in neuronal plasticity. The extensive synaptic co-localization of alpha- and beta-SYN might indicate functional redundancy of these highly homologous synucleins. However, alpha-SYN was the only family member identified in Lewy bodies and cytoplasmic inclusions characteristic for multiple system atrophy. Moreover, alpha-SYN was genetically linked to familial Parkinson's disease. The two Parkinson's disease-associated mutations accelerated the intrinsic aggregation property of alpha-SYN in vitro. Post-translational modifications, such as phosphorylation and proteolysis, and/or interaction with other proteins, might regulate alpha-SYN fibril formation in vivo. Cytoskeletal elements and signal transduction intermediates have been recently identified as binding partners for alpha-SYN. Preliminary data available from transgenic mice suggest that (over)expressed human alpha-SYN proteins are less efficiently cleared from the neuronal cytosol. Thus, Parkinson's disease-associated mutations might perturb axonal transport, leading to somal accumulation of alpha-SYN and eventually Lewy body formation.

Amino Acid Sequence↗
PubMedDate not supplied

[Excitatory amino-acids, a new class of neurotransmitters. Pharmacology and functional properties].

The pharmacology of excitatory amino acids (EAA) like glutamate or aspartate, has defined three main types of receptors: NMDA, quisqualate (now named AMPA) and kaïnate receptors, associated to cationic channels. The NMDA receptor, the best characterized, is a macromolecular complex with multiple specific sites: the agonist binding site (glutamate, aspartate, NMDA); the glycine site and polyamine site mediating allosteric regulations; the site located inside the channel for activity-dependent antagonists (phencyclidine, MK-801). This channel, permeable to calcium, is blocked by magnesium in a voltage-dependent manner. The structural complexity of the NMDA receptor suggests the existence of subtle regulations, but also offers many targets for pharmacological drugs. The calcium influx induced by NMDA receptor stimulation may account for the diversity of its functional properties. First, NMDA receptors modulate neuronal plasticity during the development and even long after. Indeed, NMDA receptor can induce long term potentiation (LTP; an experimental model of synaptic facilitation) and are involved in learning and memory. On the other hand, when over-stimulated, they induce neurotoxicity. The death of the cell occurs after several hours, during which NMDA antagonists can prevent irreversible damages. EAA systems are distributed in the whole brain, interacting with numerous other neurotransmitters, but particularly concentrated in the cortico-striatal and cortico-cortical fibers and in the hippocampus. Several neuro-psychiatric disorders could be related to a glutamatergic dysfunction: acute neuronal lesions (stroke, viral disease like AIDS) and epilepsy; but also chronic neurodegenerative disorders (Alzheimer's dementia, Huntington and Parkinson diseases). A glutamatergic hypothesis of schizophrenia arose from the phencyclidine model of psychosis, arguing for an imbalance between glutamate and dopamine. The therapeutic perspectives of glutamatergic substances in these diseases will be discussed.

Amino Acids↗
PubMed1988

Influence of T cells on the expression of lymphokine-activated killer cell activity and in vivo tissue distribution.

Lymphokine-activated killer (LAK) cells are currently being evaluated in several cancer centers for the immunotherapy of patients with a variety of cancers. Understanding the in vivo distribution of LAK cells should help to optimize their antitumor efficacy. As a model system to examine this issue, nylon wool column-passed rat lymphocytes were cultured in the presence of rIL-2 for 1 and 2 days. The resulting cells were divided into two populations; one that adhered to the plastic flasks and the second which did not adhere. The adherent cells were found to be highly cytotoxic against NK-sensitive and NK-resistant targets, whereas the nonadherent cells were unable to kill NK-resistant targets unless T cells were removed from this population. These results indicate that T cells present in IL-2 activated bulk splenocytes may interfere with the activity of LAK cells. Adherent or nonadherent LAK cells were evaluated for their pattern of in vivo distribution after i.v. inoculation. These cells were found to display a restricted pattern of distribution, localizing mainly in the lungs at 2 h after i.v. injection but redistributing into the liver and the spleen by 24 h. LAK cells were rarely recovered from the lymphoid tissues, including the peripheral lymph nodes and the mesenteric lymph nodes. However, if T cells were not removed from the LAK cell population, some radioactivity was recovered from the peripheral and mesenteric lymph nodes. Fractionation of 2 day-activated, nonadherent population on discontinuous Percoll resulted in the enrichment of large granular lymphocyte (LGL)/LAK activity in low density fractions (42% and 45% Percoll), whereas high density fraction (70% Percoll) contained T cells which showed no cytolytic activity. Upon transfer into syngeneic rats, the 42% fraction showed typical LAK migration. In contrast, the 70% fraction showed typical T cell migration. What is more important, removal of the granulated cells resulted in a population which have no granules and resemble large agranular lymphocytes known to be pre-LGL/LAK cells. Large agranular lymphocytes showed a pattern of distribution different from both T and LGL/LAK cells.

Animals↗
PubMed1985

Stability and utility of the unique human small cell carcinoma line SHP-77.

The human small cell (oat cell) carcinoma line, SHP-77, established by Fisher and Paulson in 1977 and originally described as a "large cell variant of oat cell cancer" has been evaluated by several different parameters and shown even after more than 200 passages to retain properties described for the original cell line. Karyotypic, histological, and biochemical features are retained, as well as tumorigenicity in nude mice. The original authors' suggestion that this is a propitious cell line for both in vitro and in vivo studies is supported by this report. Modulation of growth characteristics in vivo (in xenografts) emphasizes the plasticity of this unique line which serves as a valuable model for basic as well as therapeutic studies. SHP-77 can serve as an in vitro target in 51Cr and 111In release cytotoxicity assays as well as in in vivo nude mouse assays for evaluating immune reactivity of cells and serum from lung cancer patients. The potential histological variability of SHP-77, despite its biochemical stability, calls attention to the inadequacy of histological criteria for lung tumor classification.

Animals↗
PubMed1982

Amplification of natural killer activity of mouse lymphocytes by vincristine.

The possible influence of Vincristine (VCR) on NK-mediated cytolysis has been studied pretreating effector (E) or target (T) cells with the drug or adding the agent to E + T mixture during the 18-hour assay. Substantial increase of cytotoxicity was found when VCR was added to E + T cells, but not when effector or target cells were pretreated with the drug. This phenomenon was confirmed with effector splenocytes of various strains of mice, including athymic nude donors deprived of plastic-adherent or nylon-wool adherent accessory cells. Moreover, the agent did not produce irreversible inactivation of the suppression activity of splenocytes collected from DBA/2 donors infected with Friend leukaemia virus.

Animals↗
PubMed1986

Red blood cell targeting to smooth muscle cells.

Monoclonal antibody discriminating between endothelial and smooth muscle cells is suggested to be used as a vector for directed transport of drugs to injured (denuded) areas of blood vessel wall. An in vitro model system was used in the studies: vascular smooth muscle or endothelial cells grown on plastic surface were treated with specific mouse monoclonal antibody recognizing an antigen localized on the surface of smooth muscle rather than endothelial cells; then erythrocytes coated with secondary (rabbit antimouse) antibodies were added. The results were analyzed spectrophotometrically or with scanning electron microscopy. Under the experimental conditions, erythrocytes, possible 'containers' for carrying the drugs, were found to bind only to smooth muscle cells. The data show that antibody provides absolute discrimination between endothelial and smooth muscle cells and, thus, may be used as a vector for drug targeting.

Animals↗
PubMed2001

Evidence that post-tetanic potentiation is mediated by neuropeptide release in Aplysia.

Many neuromuscular and central synapses exhibit activity-dependent plasticity. The sustained high-frequency firing needed to elicit some forms of plasticity are similar to those often required to release neuropeptides. We wanted to determine if neuropeptide release could contribute to post-tetanic potentiation (PTP) and chose neuromuscular synapses in buccal muscle I3a to explore this issue. This muscle is innervated by two motor neurons (termed B3 and B38) that show PTP in response to tetanic stimulation. B3 and B38 use glutamate as their fast transmitter but express different modulatory neuropeptides. B3 expresses FMRFamide, a neuropeptide that only slightly increases its own excitatory junction potentials (EJPs). B38 expresses the small cardioactive peptide (SCP), a neuropeptide that dramatically increases its own EJPs. It was our hypothesis that SCP released from B38's terminals during tetanic stimulation mediated a component of PTP for B38. Because no antagonist to SCP currently exists, we used several indirect approaches to test this hypothesis. First, we studied the effects of increasing stimulation frequency during the tetanus or lowering temperature on PTP. Both of these changes are known to dramatically increase SCP release. We found that increasing the frequency of stimulation increased PTP for both neurons; however, the effects were larger for B38. Decreasing the temperature tended to reduce PTP for B3, while increasing PTP for B38. These results were consistent with known properties of SCP release from B38. Next we selectively superfused the neuromuscular synapses with exogenous SCP to determine if this would occlude the effects of SCP released from B38 during a tetanus. We found that exogenous SCP dramatically reduced PTP for B38 but had little effect on PTP for B3. Thus our results support the hypothesis that physiological stimulation of B38 elicits PTP that is predominantly dependent on the release of SCP from its own terminals. They also demonstrate that the mechanisms underlying PTP can be very different for two motor neurons innervating the same target muscle.

Animals↗
PubMed1991

Where practice makes perfect in texture discrimination: evidence for primary visual cortex plasticity.

In terms of functional anatomy, where does learning occur when, for a basic visual discrimination task, performance improves with practice (perceptual learning)? We report remarkable long-term learning in a simple texture discrimination task where learning is specific for retinal input. This learning is (i) local (in a retinotopic sense), (ii) orientation specific but asymmetric (it is specific for background but not for target-element orientation), and (iii) strongly monocular (there is little interocular transfer of learning). Our results suggest that learning involves experience-dependent changes at a level of the visual system where monocularity and the retinotopic organization of the visual input are still retained and where different orientations are processed separately. These results can be interpreted in terms of local plasticity induced by retinal input in early visual processing in human adults, presumably at the level of orientation-gradient sensitive cells in primary visual cortex.

Discrimination, Psychological↗
PubMed2004

Differential calcium-dependent modulation of NMDA currents in CA1 and CA3 hippocampal pyramidal cells.

Neuronal Ca2+ influx via NMDA receptors (NMDARs) is essential for the development and plasticity of synapses but also triggers excitotoxic cell death when critical intracellular levels are exceeded. Therefore, finely equilibrated mechanisms are necessary to ensure that NMDAR function is maintained within a homeostatic range. Here we describe a pronounced difference in the modulation of NMDA currents in two closely related hippocampal cell types, the CA1 and the CA3 pyramidal cells (PCs). Manipulations that increase intracellular Ca2+ levels strongly depressed NMDA currents in CA3 with only minor effects in CA1 PCs. Furthermore, activation of G(q)-coupled metabotropic receptors potentiated NMDA currents in CA1 PCs but depressed them in CA3 PCs. Interestingly, the CA3 type modulation of NMDARs could be converted into CA1-like behavior, and vice versa, by increasing Ca2+ buffering in CA3 cells or decreasing Ca2+ buffering in CA1 cells, respectively. Our data suggest that a differential Ca2+ sensitivity of the regulatory cascades targeting NMDARs plays a key role in determining the direction and magnitude of NMDA responses in various types of neurons. These findings may have important implications for NMDA receptor-dependent synaptic plasticity and the differential sensitivity of CA1 and CA3 PCs to NMDAR-dependent ischemic cell death.

Animals↗
PubMed2006

Androgen modulation of hippocampal synaptic plasticity.

This review briefly summarizes recent developments in our understanding of the role of androgens in maintaining normal hippocampal structure. Studies in rats and vervet monkeys have demonstrated that removal of the testes reduces the density of synaptic contacts on dendritic spines of cornu ammonis 1 (CA1) pyramidal neurons. This effect is rapidly reversed by treatment with either testosterone or the non-aromatizable androgen dihydrotestosterone, suggesting that maintenance of normal synaptic density is androgen-dependent, via a mechanism that does not require intermediate estrogen biosynthesis. Similar effects of these androgens are observed in ovariectomized female rats, except that in the female the actions of testosterone include a substantial contribution from estrogen formation. The ability to stimulate hippocampal spine synapse density is not directly related to systemic androgenic potency: thus, weak androgens such as dehydroepiandrosterone exert effects that are comparable to those of dihydrotestosterone; while partial agonist responses are observed after injection of the synthetic antiandrogen, flutamide. These data provide a morphological counterpart to observations that androgens enhance cognitive function and mood state, suggesting that these effects may result at least in part from hippocampal neurotrophic responses. The unusual specificity of these responses raises the possibility that effects of androgens on the brain may be mediated via different mechanisms than the masculinizing actions of these steroids in non-neural androgen target organs.

Androgens↗